System and method for estimating and manipulating estimated radiation dose

ABSTRACT

Methods are provided for permitting manipulation of an achievable dose distribution estimate deliverable by a radiation delivery apparatus for proposed treatment of a subject. One such method comprises: determining a dose modification voxel for which it is desired to modify the dose value and a corresponding magnitude of desired dose modification; for each of a plurality of beams: (i) characterizing the beam as a two-dimensional array of beamlets, wherein each beamlet is associated with a corresponding intensity value and a ray line representing the projection of the beamlet into space; and (ii) identifying one or more dose-change beamlets which have associated ray lines that intersect the dose modification voxel; modifying the intensity values of at least one of the dose-change beamlets; and updating the achievable dose distribution estimate to account for the modified intensity values of the at least one of the dose-change beamlets.

RELATED APPLICATIONS

This application claims priority from, and claims the benefit under 35USC 119(e) of, U.S. application No. 61/398,286 filed 22 Jun. 2010 whichis hereby incorporated herein by reference.

TECHNICAL FIELD

The invention relates to planning and delivery of radiation. Particularembodiments provide methods and systems for planning and delivering doesdistributions for radiation therapy.

BACKGROUND

Radiation is used in the treatment of cancer as well as some othermedical conditions. When radiation interacts with tissue, energy fromthe radiating particles is transferred and deposited within the tissue.The energy is normally deposited in the vicinity of the transfer. Themaximum deposition is normally close to the point of interaction. Theenergy deposited causes damage to cells that may eventually lead to celldeath. The quantity of energy deposited is normally described asradiation dose and has the units of Gray (Gy). 1 Gray is equal to 1Joule per kilogram of medium. The primary goal of radiation treatment isto eradicate cancerous cells in a subject by depositing sufficientradiation dose.

Radiation dose can damage or kill both cancerous and healthy tissuecells. It is typical that some healthy tissue will receive radiationdose during a radiation treatment. For example, a radiation beamoriginating from a radiation source and projecting through a subjectwill deposit radiation dose along its path. Any healthy tissue locatedwithin the path will normally receive some radiation dose. Additionally,some radiation dose will typically be deposited outside of the beam pathinto healthy tissue due to radiation scatter and other radiationtransport mechanisms. One of the challenges of radiation therapy is todeposit dose in cancerous tissue while minimizing dose received byhealthy tissue. Furthermore, some healthy tissues are more sensitive toradiation dose than others making it more important to avoid radiationdose in those tissues.

Modern radiation delivery systems are capable of delivering complex dosedistributions. There is a desire for the radiation therapy clinician tobe capable of evaluating, determining and/or optimizing trade-offsbetween delivering dose to a tumor and minimizing dose delivered tohealthy tissue. Current techniques for evaluating these trade-offs(treatment plan optimization, for example) are cumbersome and disconnectthe operator from quick and direct manipulation and evaluation ofachievable dose distributions. There is a desire for improvement ofsystems and methods for estimating achievable dose distributions andpossibly improving the evaluation of trade-offs between radiation doseto cancerous and healthy tissue.

SUMMARY

The following embodiments and aspects thereof are described andillustrated in conjunction with systems, tools and methods which aremeant to be exemplary and illustrative, not limiting in scope. Invarious embodiments, one or more of the above-described problems havebeen reduced or eliminated, while other embodiments are directed toother improvements.

One aspect of the invention provides a method for permittingmanipulation of an achievable dose distribution estimate deliverable bya radiation delivery apparatus for proposed treatment of a subject, theachievable dose distribution estimate defined over a three-dimensionalrange of voxels with a dose value for each voxel. The method comprises:determining a dose modification voxel for which it is desired to modifythe dose value and a corresponding magnitude of desired dosemodification; for each of a plurality of beams: (i) characterizing thebeam as a two-dimensional array of beamlets, wherein each beamlet isassociated with a corresponding intensity value and a ray linerepresenting the projection of the beamlet into space; and (ii)identifying one or more dose-change beamlets which have associated raylines that intersect the dose modification voxel; modifying theintensity values of at least one of the dose-change beamlets; andupdating the achievable dose distribution estimate to account for themodified intensity values of the at least one of the dose-changebeamlets.

Another aspect of the invention provides a method for permittingmanipulation of an achievable dose distribution estimate deliverable bya radiation delivery apparatus for proposed treatment of a subject, theachievable dose distribution estimate defined over a three-dimensionalrange of voxels with a dose value for each voxel. The method comprises:determining a dose modification voxel for which it is desired to modifythe dose value and a corresponding magnitude of desired dosemodification; for each of a plurality of beams: (i) characterizing thebeam as a two-dimensional array of beamlets, wherein each beamlet isassociated with a corresponding intensity value; (ii) associating a rayline with each voxel, the ray line projecting from the voxel andintersecting the two dimensional array of beamlets; and (iii)identifying a dose-change beamlet to be the beamlet intersected by theray line associated with the dose modification voxel; modifying theintensity values of one or more of the dose-change beamlets; andupdating the achievable dose distribution estimate to account for themodified intensity values of the one or more of the dose-changebeamlets.

Another aspect of the invention provides a method for estimating a dosedistribution over a three-dimensional range of voxels resulting from abeam having a spatially varying two-dimensional intensity distributioncharacterized by a two-dimensional array of beamlets wherein eachbeamlet is associated with a corresponding intensity value. The methodcomprises: associating a ray line with each beamlet, the ray linerepresenting the projection of the beamlet into space; convolving thetwo-dimensional intensity distribution with a two-dimensional doseestimate kernel to obtain a two-dimensional convolved intensitydistribution, the two-dimensional convolved intensity distributioncomprising a convolved intensity value for each beamlet; and for eachbeamlet in the two-dimensional array of beamlets: identifying voxels inthe three-dimensional range of voxels that are intersected by the rayline associated with the beamlet; and adding a dose contribution to theintersected voxels, the dose contribution based on the convolvedintensity value of the beamlet.

Other aspects of the invention provide systems comprising one or morecontrollers configured to perform the methods of various embodiments ofthe invention. Other aspects of the invention provide computer programproducts carrying instructions embodied in a non-transitorycomputer-readable medium, the instructions when executed by a suitableprocessor cause the processor to perform the methods of variousembodiments of the invention. Other aspects of the invention providemethods, systems and/or computer program products that use the methodsof various embodiments for planning and/or delivery of radiationtreatment to subjects.

In addition to the exemplary aspects and embodiments described above,further aspects and embodiments will become apparent by reference to thedrawings and by study of the following detailed descriptions.

BRIEF DESCRIPTION OF DRAWINGS

Exemplary embodiments are illustrated in referenced figures of thedrawings. It is intended that the embodiments and figures disclosedherein are to be considered illustrative rather than restrictive. Indrawings which illustrate non-limiting embodiments:

FIG. 1 schematically depicts an example radiation delivery apparatusthat may be used in delivering radiation dose to a subject;

FIG. 2 schematically depicts another example radiation deliveryapparatus that may be used in delivering radiation dose to a subject;

FIG. 3 is a flowchart depicting a method for treatment planningcomprising an optimization process which is suitable for use withintensity modulated radiation treatment according to a particularembodiment;

FIG. 4A is a flowchart depicting a method for planning radiationtreatment and treating a subject using radiation therapy involvinggenerating, and permitting operator manipulation of, estimated dosedistribution according to a particular embodiment of the invention.

FIG. 4B is a flowchart depicting a method for generating, and permittingoperator manipulation of, an estimated dose distribution according to aparticular embodiment.

FIG. 4C is a flowchart depicting an initialization method suitable foruse in the method of FIG. 4B.

FIG. 4D is a flowchart depicting a dose-estimation update method fordetermining the changes in estimated dose distribution which may be usedwith the method of FIG. 4B according to a particular embodiment.

FIG. 5A shows a schematic depiction of a two-dimensional cross sectionof a calculation grid superimposed on image data which includesexemplary healthy tissue and target structures together with theestimated dose for each voxel in the calculation grid. FIG. 5B shows adose volume histogram (DVH) corresponding to the FIG. 5A dosedistribution.

FIG. 6 is an illustration of a beam between a radiation source andsubject including associated intensity grid and example ray lines.

FIG. 7A shows an example of an operator communicating a desired dosechange directly on a representation (e.g. a graphical representation) ofa dose distribution. FIG. 7B shows a cross-section of the updated dosedistribution determined in accordance with the method of FIG. 4B as aresult of the FIG. 7A desired dose change.

FIG. 8A shows an example of an operator communicating a desired dosequality metric change on a representation (e.g. a graphicalrepresentation) of a DVH. FIG. 8B shows the updated DVH determined inaccordance with the method of FIG. 4B as a result of the FIG. 8A desireddose change.

FIG. 9A shows the dose modification voxels determined in accordance withthe method of FIG. 4B and corresponding to the FIG. 8A desired dosequality metric change. FIG. 9B shows a cross-section of the updated dosedistribution determined in accordance with the method of FIG. 4B as aresult of the FIG. 9A desired dose change.

FIG. 10 shows an example of an operator communicating a desired dosequality metric change on a representation (e.g. a graphicalrepresentation) of a biological index.

FIG. 11A shows the dose modification voxels determined in accordancewith the method of FIG. 4B and corresponding to the FIG. 10 desired dosequality metric change. FIG. 11B shows a cross-section of the updateddose distribution determined in accordance with the method of FIG. 4B asa result of the FIG. 11A desired dose change.

FIG. 12 schematically depicts an example of a dose update gridillustrative of a technique which may be used to update the dosedistribution as part of the method of FIG. 4B according to a particularembodiment.

FIG. 13 is a schematic illustration of a method for rapid estimation ofachievable dose distribution according to a particular embodiment.

FIG. 14 schematically depicts a 360° trajectory, a plurality of beams atangularly evenly spaced locations around the trajectory, ray linesintersecting a centrally located voxel and a two-dimensionalcross-section of a dose update grid estimated to be achievable by theplurality of beams.

FIG. 15 depicts an example profile of the FIG. 14 achievable dose updategrid intersects the dose modification voxel.

FIG. 16 depicts a dose update grid which is the same as the FIG. 14 doseupdate grid except that it has been translated to a different dosemodification voxel.

FIG. 17 is a schematic depiction of a system for estimation andmanipulation of estimated dose according to a particular embodiment ofthe invention.

FIGS. 18A-18C schematically depict a number of radial modification dose(RMD) distributions and how various angular ranges of RMDs can beobtained by combining other angular ranges of RMDs.

FIG. 19A is a three-dimensional rendering showing a target structure anda healthy tissue structure. FIG. 19B is a cross-sectional view bisecting(and showing outlines of) the target structure and healthy tissuestructure of FIG. 19A.

FIG. 20A shows a representation of a cross-section of an initialestimated dose distribution for the FIG. 19A tissue structures. FIG. 20Bshows an initial DVH for the FIG. 19A tissue structures.

FIG. 21A shows a magnified portion of the FIG. 20B target structure DVHand operator manipulation thereof. FIG. 21B shows a number of dosemodification distributions resulting from the FIG. 21A operatormanipulations. FIG. 21C shows an updated dose distribution and updatedtarget and healthy structure DVHs after the FIG. 21A manipulation.

FIG. 22A shows operator manipulation of the FIG. 20B healthy tissue DVH.

FIG. 22B shows a number of dose modification distributions resultingfrom the FIG. 22A operator manipulations. FIG. 22C shows updated targetand healthy structure DVHs after the FIG. 22A manipulation.

FIG. 23A shows two example dose modification distributions used tocorrect the FIG. 22C violation of the constraint on the target dosedistribution. FIG. 23B shows target structure DVH after application ofthe FIG. 23A dose modification distributions. FIG. 23C shows arepresentation of the resultant cross-sectional dose distribution.

FIG. 24A shows DVHs for target and healthy tissue structures at theconclusion of a series of dose modifications by the operator. FIG. 24Bshows a cross-sectional estimated dose distribution corresponding to theDVHs of FIG. 24A.

DESCRIPTION

Throughout the following description specific details are set forth inorder to provide a more thorough understanding to persons skilled in theart. However, well known elements may not have been shown or describedin detail to avoid unnecessarily obscuring the disclosure. Accordingly,the description and drawings are to be regarded in an illustrative,rather than a restrictive, sense.

FIG. 1 schematically depicts an example radiation delivery apparatus 10containing a radiation source 111 for delivery of radiation to a subject110 (e.g. a cancer patient). In some embodiments, radiation source 111may comprise, or may be generated by, a linear accelerator. In general,radiation source 111 may be generated using any suitable technique. Forexample, radiation source 111 may comprise decaying matter (e.g.Cobalt-60 or the like) or other types of source(s) which may emitradiation comprising neutrons, electrons, protons, other chargedparticles and/or the like.

In the exemplary FIG. 1 radiation delivery apparatus 10, radiationsource 111 is mounted to a gantry 112 and subject 110 is placed on table113. Gantry-mounted radiation source 111 and table 113 with subject 110may rotate and/or translate with respect to each other. For example,gantry 112 may rotate about a longitudinal axis 114 and table 113holding subject 110 may rotate about a vertical axis 115. Table 113 mayalso translate relative to gantry 112 and source 111 in one or more ofthe three dimensions shown by axes 116. Radiation from a radiationsource may be emitted in all directions. An enclosure 117 surrounds mostof radiation source 111, so that the majority of radiation emitted bysource 111 is absorbed within enclosure 117.

Radiation emitted toward subject 110 is permitted to pass throughenclosure 117 and through a beam-shaping system 118. Beam-shaping system118 may comprise one or more collimators which may be used to define abeam of radiation that emanates from radiation source 111 and intosubject 110. The collimators of beam-shaping system 118 may be motorizedand their position and/or movement may be controlled (e.g. by a suitablyconfigured computer control system or the like). The collimators ofbeam-shaping system 118 may be controllably configured so that the shapeof the radiation beam entering subject 110 preferentially intersectscancerous tissue. In the illustrated example radiation deliveryapparatus 10 of FIG. 1, beam-shaping system 118 comprises a multi-leafcollimator (MLC) 118A having a plurality of individually controllableleaves. MLC 118A may also be controllably moved to rotate about beamaxis 119.

The FIG. 1 exemplary radiation delivery apparatus 10 can be used todeliver radiation therapy treatment to subject 110. A number oftechniques are known for using radiation delivery apparatus 10 inmanners which attempt to provide desired dose to diseased tissue (e.g.cancerous tumor) while attempting to minimize the dose to healthytissue. A first such technique involves moving gantry 112 and/or table113 to a configuration wherein the radiation beam emitted from source117 preferentially passes through relatively more diseased tissue andrelatively less healthy tissue. This first technique may be improved bytreating subject 110 with a first beam at a first configuration ofgantry 112 and table 113, moving the gantry 112 and table 113 relativeto one another, and then treating subject 110 with a second beam whichprojects from a different direction than the first beam. Using thistwo-beam technique, the diseased tissue (tumor) may receive a dose thatis a combination of the dose from the two beams, while much of thehealthy tissue surrounding the tumor would receive dose from primarily asingle one of the beams. This two-beam technique may be extended tomultiple (e.g. more than two) beams. Each different relative orientationof gantry 112 and table 113 may correspond to a different beam directionand may be referred to simply as a “beam”.

Another example of a technique for using radiation delivery apparatus 10in a manner which attempts to provide desired dose to a tumor ofdiseased tissue while minimizing dose to healthy tissue involvescollimating each radiation beam (i.e. the beam from each relativeconfiguration of gantry 112 and table 113) so that the projection of thetumor from the view of the radiation source (Beam's eye view) closelyapproximates the outline of the tumor. In this way dose to healthytissue surrounding the tumor will be reduced. Collimation system 118(e.g. MLC 118A) may be used to collimate the individual beams. Thiscollimation technique may be improved by selectively (partially orfully) blocking portions of a radiation beam (from a first direction)that intersect both tumor and sensitive healthy tissue and thencompensate for the blocked portion of the tumor by selectively(partially or fully) unblocking portions of one or more radiation beamsfrom one or more other directions. A radiation beam (from a particulardirection) comprising spatially non-uniform transmitted portions may bereferred to as “Intensity Modulated” in reference to the spatiallyvarying intensity of radiation across the two-dimensional beamprojection. Intensity modulation can further improve the differencebetween dose received by healthy tissue and dose received by tumor,particularly in circumstances where some healthy tissue is of relativelyhigh importance (e.g. healthy organs) and/or is in relatively closeproximity to the target tissue and it is desired to impart even lessdose to such highly important tissues.

In accordance with other techniques, it may be beneficial to dynamicallymove one or more components of radiation delivery apparatus 10 duringthe delivery of radiation. For example, collimation system 118 canchange the shape of a radiation beam while source 117 is emittingradiation, thereby providing dynamically varying collimation shapes forintensity modulation. Additionally or alternatively, gantry 112 andtable 113 can move relative to one another while source 117 is emittingradiation, thereby providing continuously varying beam directions (incontrast to a finite number of discrete beam directions). Sometechniques may involve dynamically varying the position of radiationsource 117 through a motion trajectory (e.g. relative movement of gantry112 and table 113) while simultaneously dynamically varying thecollimated beam shape and/or the intensity of radiation source 117.

Radiation delivery apparatus 10 represents only one example of aradiation delivery apparatus. Other types of radiation deliveryapparatus may be used to deliver therapeutic radiation to a subject. Anumber of non-limiting examples of radiation delivery apparatus includeCyberKnife™ (Accuracy Incorporated), Tomotherapy™ (TomotherapyIncorporated) and Gammaknife™ (Elekta AB). FIG. 2 schematically depictsan example of a Tomotherapy™ radiation delivery apparatus 12. Inapparatus 12, radiation source 121 moves in a toroid-shaped gantry 122about subject 120 who is laying on table 123. Subject 120 and table 123may be translated relative to gantry 122 (and/or gantry 122 may betranslated relative to subject 120 and table 123) in one or more of thedirections indicated by axes 124. For example, table 123 may be movedinto and out of gantry 122 while radiation source 121 moves incircumferential direction(s) 125 within gantry 122. Radiation emitted bysource 121 may project through collimation system 126 (e.g. a MLC 126Aor the like). Collimation system 126 may move circumferentially (withsource 121) within gantry 122 to create a fan beam 127 impinging onsubject 120. As source 121 and collimation system 126 move incircumferential directions 125 around subject 120, table 123 and subject120 may move relative to gantry 120 and MLC 126A may be configured toprovide intensity modulated beams from varying directions around subject120.

Using radiation delivery apparatus (like exemplary apparatus 10, 12 ofFIGS. 1, 2) to deliver therapeutic radiation treatment involvestreatment planning. Treatment planning may involve determining theinformation used to control the radiation delivery apparatus duringradiation delivery. Such information may include, by way of non-limitingexample, beam configuration parameters (e.g. a number of beams,directions of beams, radiation energy and/or the like) and beam deliveryparameters (e.g. collimation shape(s) and corresponding collimationsystem configuration(s), radiation intensity(s) and/or the like).

Since the size, shape and position of a tumor with respect to thesurrounding healthy tissue are different for each subject, a diagnosticimaging procedure is typically used prior to (or as a part of) treatmentplanning for the purposes of determining the spatial locations ofdiseased and healthy tissue. Computed Tomography (CT), MagneticResonance Imaging (MRI) and Positron Emission Tomography (PET) arecommon imaging methods used for this diagnostic imaging process. Theresult of CT, MRI and PET imaging may comprise 3-dimensional imageswhich contain anatomical and functional information. In someembodiments, diagnostic imaging may involve procuring 4-dimensionalimages, which incorporate time varying image information (e.g. toaccount for breathing).

The locations of diseased and healthy tissue may be identified on theseimages prior to (or as a part of) treatment planning. Identification ofthe locations of diseased and healthy tissue can be performed manuallyalthough methods for automatic and semi-automatic identification mayalso be used. Treatment planning may involve using well known methods tomodel the radiation dose resulting from a radiation beam. The dose thata subject would receive from a particular radiation beam may beevaluated by overlaying the dose distribution modeled for the particularradiation beam on the subject's images. The dose that a subject wouldreceive from a proposed treatment plan (e.g. a plurality of radiationbeams) may be evaluated by superposing dose distributions modeled forthe individual beams of the plan and overlaying the superposed dosedistribution on the subject's images.

A proposed treatment plan may be characterized or otherwise specified bya set of radiation delivery parameters. As used in this specificationand the accompanying claims, radiation delivery parameters may comprise:beam configuration parameters which may relate to the geometricpositioning of the radiation source with respect to the subject (e.g.numbers of beams, directions of beams, radiation energy of beams, motionof beams (e.g. for continuously varying beams) and/or the like) and/orbeam delivery parameters which may relate to the characteristics of oneor more beam configurations (e.g. collimation shape(s) and correspondingcollimation system configuration(s), motion of collimation shape(s) andcorresponding collimation system configuration(s) (e.g. for continuouslyvarying collimation shapes), radiation intensity(s), and/or the like).By estimating/modeling the dose distributions from multiple differenttreatment plan proposals (as characterized by multiple correspondingsets of radiation delivery parameters), the multiple different treatmentplan proposals can be compared against one another. Once a proposedtreatment plan is selected (e.g. because it is determined to be superiorto others or is otherwise determined to be satisfactory), the radiationdelivery parameters associated with the selected treatment plan may betransferred to the radiation delivery apparatus for delivery of theselected treatment plan to the subject.

Treatment planning for intensity modulated radiation therapy (IMRT) maybe more complex because of the permissible spatial variation ofintensity distribution across a two-dimensional cross section of eachbeam or each portion of a beam. Because of the spatial varying intensitydistributions of beams associated with IMRT, IMRT treatment planningtypically involves dividing each beam into a two-dimensional matrix ofspatially varying intensity portions which may be referred to asbeamlets. Each beamlet may be effectively treated as a separate beamelement that follows a ray line from the source into the subject. In atypical non-limiting IMRT plan, there may be 5 to 9 beams each with amatrix that may comprise more than 100 beamlets.

IMRT planning by a human observer is normally considered impractical dueto the large number of beamlets. Several computer algorithms have beendeveloped to determine the spatially varying intensity distributions ofeach beam in IMRT plans—e.g. the intensities for each of the beamlets ineach portion of each beam of the IMRT plan. These algorithms typicallyinvolve iterative optimization. For example, at each iteration, aparticular set of radiation delivery parameters is proposed, thecorresponding dose distribution is calculated (e.g. modeled) and thecorresponding dose distribution is evaluated by comparing a qualitymetric associated with the corresponding dose distribution to someobjective. The next iteration may then attempt to propose a set ofradiation delivery parameters whose dose distribution is superior to theprevious iteration (when evaluated in relation to the same objective).The iterative process normally repeats until an optimization terminationcriterion is achieved. The iterative optimization process may berelatively time consuming, computationally expensive and/or temporallyinefficient, because of the need to model/calculate a dose distributionat each iteration.

FIG. 3 schematically depicts a method 14 for treatment planning suitablefor use with IMRT according to a particular embodiment. Method 14commences in block 130 which involves delineating target (e.g. diseased)tissue and healthy tissue within the subject using whatever diagnosticimage information may be available. In some embodiments, block 130 mayinvolve sub-dividing healthy tissue into one or more levels ofrelatively important healthy tissue (e.g. organs) and relatively lessimportant healthy tissue. In some embodiments, block 130 may involveacquiring image information from (or through effecting) an imagingprocedure. Such image information may be obtained by any suitabletechnique, including (without limitation): Computed Tomography (CT),Magnetic Resonance Imaging (MRI), Positron Emission Tomography,Ultrasound and/or any other suitable imaging procedure. The imageinformation may be used in block 130 to determine spatial anatomical andfunctional information regarding diseased and healthy tissue in thesubject. This delineation between target and healthy tissues andstructure identification may be performed manually, by an operator,and/or using automatic or semi-automatic image segmentation methods.

Block 131 involves specifying dose objectives for target and healthytissues. Ideally, the dose objectives might be: (i) 100% of the tumorvolume receives at least the prescription dose; (ii) 0% of the tumorvolume receives dose greater than the prescription dose; and (iii) 0% ofthe healthy tissue volume receive any dose. Such an ideal objective isnot realizable in practice. Instead, achieving a prescription dose tothe tumor must be balanced against providing a low dose to healthytissue structures. Also, there are commonly many healthy tissuestructures of concern that vary in importance which can make the numberof possible trade-offs cumbersome. By way of non-limiting example: ahealthy tissue objective may comprise maximum 20% of the healthy tissuestructure volume receives 30% of the dose prescribed to the target; anda target tissue objective may comprise minimum of 90% of the tumortarget volume receives 95% of the dose prescribed to the target. Block131 may also involve specifying a dose quality metric which may be usedto evaluate proposed treatment plan iterations against the block 131dose distribution objectives. Such dose quality metrics may additionallyor alternatively be used to indirectly specify dose distributionobjectives.

Method 14 then proceeds to block 132 which involves performing aniterative optimization process to arrive at a set of radiation deliveryparameters. A typical iterative optimization process which may beimplemented as a part of block 132 was discussed above. At theconclusion of the block 132 iterative optimization process, method 14proceeds to block 133 which involves evaluating the treatment plan (e.g.the calculated/modeled dose distribution) which results from using theradiation delivery parameters output by the block 132 optimization. Theblock 133 evaluation may be performed by one or more human operators. Insome embodiments, however, the block 133 evaluation may be automated.For example, constraints could be developed that specify a minimumnumber of objectives that must be achieved in order to achieve apositive block 133 evaluation. The number of achieved objectives mightbe more important for some target structures or for some specifiedhealthy tissue structures. Even in the case of an automated block 133evaluation, the resulting dose distribution would likely be evaluated bya clinician before actually delivering radiation.

If the block 131 dose distribution objectives are not achievable inpractice, then the block 132 optimization may fail to determine anacceptable treatment plan. Conversely, if the block 131 dosedistribution objectives are too easily achieved, the treatment planspecified by the block 132 optimization may not achieve the besttrade-offs that could be realized in practice. In these circumstances(block 133 NO output path), method 14 may loop back to block 131, wherea different optimization may be performed with different dosedistribution objectives. Typically, to ensure that the dose distributionachieved in treatment planning method 14 is close to optimal, it isdesirable to perform multiple block 132 optimizations with multiple setsof block 131 dose distribution objectives. Once it is determined inblock 133 that a particular plan is optimal (block 133 YES output path),then method 14 may proceed to block 134 where the radiation deliveryparameters may be transferred to the radiation delivery apparatus fordelivery to the subject.

Other methods of providing complex treatment plans and correspondingdose distributions may involve similar iterative optimization. Anycombination of radiation delivery parameters may be used in anoptimization process for deriving a treatment plan. Such complextreatment plans and corresponding dose distributions may include, by wayof non-limiting example, so-called direct aperture optimizationtechniques, radiation treatment techniques involving dynamic variationof the direction of radiation (e.g. movement of the radiation sourceduring treatment) and/or dynamic variation of collimation shapes and/orintensities within particular beams during treatment and radiationtreatment techniques using radiation delivery apparatus such asCyberKnife™ (Accuracy Incorporated), Tomotherapy (TomotherapyIncorporated) and Gammaknife™ (Elekta AB). The iterative optimizationsinvolved in treatment planning for all of these radiation deliverytechniques suffer from similar drawbacks as those discussed above forthe iterative optimization associated with IMRT treatment planning. Moreparticularly, such optimizations are time consuming and computationallyexpensive because of the need for calculating/modeling a dosedistribution at each iteration.

One aspect of the invention provides systems and methods for permittingmanipulation of achievable dose distribution estimates. In particularembodiments, estimated dose distributions and associated dose qualitymetrics may be manipulated without the cumbersome and computationallyexpensive calculations involved in simulating dose for specificradiation delivery parameters (e.g. without the need for iterativeoptimization). These methods and systems may be simple to use and maypermit operator manipulation of estimated dose distributions andassociated dose quality metrics. By way of non-limiting example, anoperator may select a graphical representation of a dose quality metricusing a computer mouse or similar computer pointing device, drag it tothe left or right, up or down as desired. As another non-limitingexample, an operator may modify a graphical representation of a dosedistribution using a computer mouse or similar computer pointing device,to “paint” or “erase” dose from a region of subject anatomy. As theseoperator-directed manipulations are made, the achievable dosedistribution estimate and corresponding dose quality metrics may beupdated in near real-time.

The range of physically achievable dose distributions may be limited.Particular embodiments involve the imposition of limits or restrictionson available manipulations, so that the estimated dose distributions(after operator manipulation) are at least approximately achievable. Inthis way operators are able to rapidly explore trade-offs between dosedelivery to target tissues (e.g. tumor(s)) and healthy tissues (e.g.organ(s)) while ensuring that the subject will ultimately receive a dosedistribution substantially similar to the estimated one.

FIG. 4A schematically depicts a method 16 for planning radiationtreatment and treating a subject using radiation therapy involvingmanipulation of estimated dose distribution according to a particularembodiment of the invention. Method 16 may generally be divided into twoparts: a first part 16A which involves planning the radiation treatmentand a second part 145 which involves delivering radiation treatment tothe subject. As discussed further herein, planning part 16A may involvedetermining radiation delivery parameters which may be provided to aradiation delivery apparatus to permit block 145 delivery of radiationin accordance with the plan.

Method 16 commences in block 141 which involves delineating target (e.g.diseased) tissue and healthy tissue within the subject using whateverdiagnostic image information may be available. Block 141 may besubstantially similar to block 130 described above for method 14 (FIG.3). Method 16 then proceeds to block 142 which involves generating andpermitting operator manipulation of an achievable dose distribution.Operator manipulation of the achievable dose distribution permitted as apart of block 142 may be analyzed directly, effectively in real-time,facilitating a rapid and more comprehensive understanding of thecompromises between target tissue dose and healthy tissue dose. Operatormanipulation of the achievable dose distribution permitted as a part ofblock 142 may comprise modification of or additions to target tissueand/or healthy tissue. Block 142 of method 16 is described in moredetail below.

At the conclusion of block 142 (e.g. where the operator is satisfiedwith the manipulated version of the achievable dose distribution orotherwise), method 16 proceeds to optional block 143 which involvesdetermining radiation delivery parameters capable of permitting aradiation delivery apparatus to deliver the estimate of achievable doseas output from block 142. Block 143 may involve performing an iterativeoptimization process or the like to derive radiation delivery parameters(e.g. beam configuration parameters and/or beam delivery parameters).The block 143 iterative optimization may involve processes similar tothose described in blocks 131 and 132 of treatment planning process 14described above (FIG. 3). The block 143 optimization may also involve anevaluation similar to that of block 133 of treatment planning process 14described above (FIG. 3). Advantageously, because of the availability ofdose distribution manipulation in block 142, it may not be necessary toperform multiple optimizations with different dose distributionobjectives as a part of block 143 or fewer optimizations with differentdose distributions may be performed as a part of block 143 when comparedto the optimization process (blocks 131, 132, 133) of method 14 (FIG.3)—i.e. the availability of dose distribution manipulation in block 142of method 16 may reduce or eliminate the need for multiple iterativeoptimization loops (analogous to loops through blocks 131, 132 and 133(NO output path) of the method 14 optimization process).

After optimization to obtain the radiation delivery parameters in block143, method 16 proceeds to block 144 which involves transferring theblock 143 radiation delivery parameters to the controller of a radiationdelivery apparatus. These radiation delivery parameters may then be usedby the controller of the radiation delivery apparatus in block 145 tocause the radiation delivery apparatus to deliver radiation to thesubject in accordance with the radiation treatment plan corresponding tothe radiation delivery parameters.

As discussed briefly above, block 142 of radiation treatment method 16involves generating, and permitting operator manipulation of, anachievable dose distribution. FIG. 4B schematically illustrates a method18 for generating, and permitting operator manipulation of, anachievable dose distribution according to a particular embodiment.Method 18 of FIG. 4B may be used to implement block 142 of radiationtreatment method 16 (FIG. 4A).

Method 18 commences with initialization in block 218. The block 218initialization may involve: establishing a calculation grid over aregion of interest in the delineated image information; defining aconfiguration of beams; defining an initial intensity distribution ofbeamlets for each beam; generating an initial estimate of an achievabledose distribution using the beam configuration and beamlet intensitydistributions; and, optionally, determining an initial estimate of oneor more dose quality metrics based on the initial estimated dosedistribution.

FIG. 4C schematically illustrates an initialization method 20 suitablefor use in block 218 of method 18 according to a particular embodiment.Initialization method 20 commences in block 40 which involves creating acalculation grid and superimposing the calculation grid over thedelineated image data and segmented healthy and target tissuestructures. The delineated image data may be obtained as a part of block141 (FIG. 4A) discussed above. The superimposed calculation grid maycomprise a three-dimensional grid of voxels that spans a region ofinterest within a subject. The three-dimensional grid of voxels may becharacterized by a suitable coordinate system which may permit indexingand/or identifying individual voxels within the grid by theircorresponding coordinates.

FIG. 5A shows a schematic depiction of a two-dimensional cross sectionalportion 151 of a three-dimensional calculation grid 151A superimposed onimage data comprising exemplary anatomical structures including healthytissue structure 152 (shown in dashed lines) and target structure 153(shown in full lines). Only two anatomical tissue structures are shownin the FIG. 5A example. In practice, there may be different numbers ofstructures (target structures and/or healthy tissue structures)associated with a region of interest in a subject. While the illustratedportion 151 of calculation grid 151A may be referred to as atwo-dimensional cross-section, each box of grid portion 151 shown inFIG. 5A actually represents a corresponding voxel in the overallthree-dimensional calculation grid 151A for the subject. In this sense,the FIG. 5A grid portion 151 is actually three-dimensional grid portion151 with a depth of one voxel. As will be explained in more detailbelow, the numerical values in each voxel of grid portion 151 representexample values of the dose distribution expected to be delivered tothese voxels, although these dose distribution estimates will nottypically be known when calculation grid is established in block 40.

Returning to FIG. 4C, initialization method 20 proceeds to block 42which involves defining a configuration of beams. The block 42 initialconfiguration of beams may comprise defining parameters similar to thosebeam configuration parameters discussed above—e.g. numbers of beams,directions of beams, radiation energy of beams and/or the like. Theblock 42 beam configuration may be identified manually or through anindependent optimization process. The block 42 beam configuration maycomprise one or more static beams, one or more continuously moving beamsor a combination of static and moving beams. Continuously moving beamsmay be characterized by a motion path (trajectory) of the beam directiontogether with a suitable sampling of multiple stationary beams withpositions along the motion path.

Initialization method 20 then proceeds to block 44 which involvesdefining an initial intensity distribution of beamlets for each of theblock 42 beams. Such initial intensity distributions may be similar toinitial values for parameters similar to beam delivery parametersdiscussed above. FIG. 6 schematically depicts a representative beam 159from the block 42 beam configuration. Beam 159 is directed from aradiation source 161 and delivered toward a subject 160. Each beam inthe block 42 beam configuration may be characterized, at least in part,by the position of radiation source 61 with respect to subject 60 (asdefined by the block 40 calculation grid and the corresponding imagedata for subject 60). Each beam 159 is associated with a correspondingintensity distribution 165 which is defined in block 44. In block 44,the intensity distribution 165 corresponding to each beam 159 may besegmented into a two-dimensional grid 162 of intensity beamlets 164. Twodimensional intensity distribution grid 162 may be characterized by asuitable coordinate system which may permit indexing and/or identifyingindividual beamlets 164 within grid 162 by their correspondingcoordinates. Each beamlet 164 may be associated with a corresponding rayline 163 which originates from radiation source 161 and passes throughintensity distribution 165 and grid 162 at the location of the beamlet164. In the FIG. 6 illustration, a particular ray line 163A is shown tocorrespond with a particular beamlet 164A.

Block 44 also involves assigning initial intensity values to theindividual beamlets 164 for each beam 159—i.e. initializing theintensity distribution 165 for each beam 159. The initial intensitydistributions 165 may be defined in block 44 using a variety ofdifferent techniques. By way of non-limiting example:

-   -   Intensity distribution 165 is zero for all beamlets 164 and all        beams 159. This initial intensity assignment corresponding to        zero dose for all structures.    -   Intensity distribution 165 is random over each grid 162 of        beamlets 164 for each beam 159, intensity of each beamlet 164 is        random over all intensity distributions 165 for all beams 159 or        some other suitable scheme involving at least some form of        random assignment of intensities to corresponding beamlets 162.    -   Intensity distributions 165 for all or a subset of beams 159 are        assigned so that an approximate sphere of dose encompasses        target structure(s) 153.    -   Intensity distributions 165 for all or a subset of beams 159 are        assigned such that beamlets 162 corresponding to ray lines 163        that intersect target structure(s) 153 are assigned an initial        positive intensity value (e.g. unity) and beamlets 162 are        otherwise assigned a different initial value (e.g. zero or some        other relatively low value).    -   Intensity distributions 165 for all or a subset of beams 159 are        rescaled (e.g. by an equal amount) so that the resultant        estimated dose distribution would have a maximum dose        corresponding to some dose threshold (e.g. a dose threshold        equal to a highest prescription dose for target structure(s)        153).    -   Intensity distributions 165 for all or a subset of beams 159 are        proportional or correlated with a desired (e.g. prescription)        dose for target structure(s) 153.        -   Intensity distributions 165 are generated for all or a            subset of beams 159 where beamlets 162 corresponding to ray            lines 163 that intersect target structure(s) 153 are            assigned an intensity value proportional to or correlated            with a desired dose for each such target structure 153.        -   A margin (e.g. offset) may be added to the intensity            distributions 165 (or to individual beamlets 162            corresponding to ray lines 163 that intersect target            structure(s) 153) to ensure proper coverage of the target            structure(s) 153 by the resulting dose distribution.        -   For target structures 153 that overlap in a given beam 159            (e.g. a ray line 163 intersects multiple target structures            153), the intensity of the corresponding beamlet 164 may be            assigned an intensity proportional to or correlated with the            desired dose for the target structure with the highest            desired dose and/or the corresponding beamlet 164 may have            its assigned intensity weighted by the target structure 153            that has the highest desired dose.        -   For target structures that overlap in a given beam 159, the            intensity of the corresponding beamlet 164 may be assigned            an intensity proportional to or correlated with the desired            dose for the target structure with the lowest desired dose            and/or the corresponding beamlet 164 may have its assigned            intensity weighted by the target structure 153 that has the            lowest desired dose.

Returning to FIG. 4C, after defining intensity distributions 165 inblock 44, method 20 proceeds to block 46 which involves generating aninitial estimate of the dose distribution based on the block 42 beamconfiguration and the block 44 intensity distributions. Block 46 mayinvolve known methods of dose estimation, such as by way of non-limitingexample, Monte Carlo, collapsed cone convolution, pencil beam,anisotropic analytical algorithm, Boltzman equation solvers and/or thelike. The block 46 dose estimation may comprise independently estimatingthe dose for each beam 159 of the block 42 beam configuration and thenadding these dose contributions to arrive at an overall initial dosedistribution estimate. The block 46 dose estimation may involveassigning a dose value to each voxel in the block 40 calculation grid151A. These dose estimate values are represented in FIG. 5A by thenumbers in the boxes corresponding to voxels, it being understood thathigher numbers correspond generally to higher estimated dose amounts.Initialization method 20 may optionally involve a procedure (in block47) for establishing an approximate relationship between the intensitiesof beamlet(s) 164 having ray line(s) 163 that intersect a particularvoxel and the corresponding dose delivered to the particular voxel. Thisblock 47 approximate relationship may be determined using one or moresuitable calibration procedures, may be determined based on empiricaltesting and/or data and/or the like. This block 47 relationship isexplained in more detail below.

Method 20 may then proceed to block 48 which involves optionallydetermining one or more initial dose quality metrics based on the block46 initial dose distribution estimate. Dose quality metrics determinedin block 48 may generally comprise any function of the estimated dosedistribution. Some dose quality metrics include:

-   -   The average dose to a structure;    -   Dose volume histogram(s)—often referred to as DVHs;    -   Rate of dose fall-off outside target structure(s) 153;    -   Dose conformity indices—e.g. how closely the prescription dose        matches the shape of target structure(s) 153);    -   Radiobiological objective(s)—e.g. tumor control probability,        normal tissue complication probability, equivalent uniform dose,        and/or the like.

DHVs represent one popular and widely used dose quality metric. A DVH isa graphical plot of structure volume (target tissue or healthy tissue)on the Y-axis versus dose on the X-axis. It is common to use cumulativeDVHs (which are typically referred to simply as ‘DVHs’) when evaluatingtreatment plans. FIG. 5B shows a plot 154 of two typical DVHscorresponding to the estimated dose distribution shown in thethree-dimensional calculation grid 151A for which a cross-sectionalportion 151 is shown in FIG. 5A. DVH 156 corresponds to target structure153 and DVH 155 corresponds to healthy tissue structure 152.

Returning to the FIG. 4B method 18 for generating and permittingmanipulation of achievable dose distributions, after completion of theblock 218 initialization, method 18 proceeds to block 220 which involvesdetermining the coordinates and estimated magnitude of desired dosemodifications. The coordinates determined in block 220 to be associatedwith desired dose changes may be referred to as the desired dosemodification coordinate(s)/voxel(s) and the associated magnitudes may bereferred to as the desired dose modification magnitude(s). Block 218 mayinvolve receiving operator input which is indicative of desired dosemodifications. By way of non-limiting example, an operator may indicatea desired dose modification (increase or decrease) to a particular dosemodification voxel in calculation grid 151A, an operator may communicatea desired modification to a dose quality metric and/or the like. Variousembodiments may comprise one or more of a variety of differenttechniques for receiving such operator input. Such techniques mayinclude (without limitation):

-   -   Keyboard entry (e.g. typing a spatial location (e.g. calculation        grid coordinates) of the desired dose modification voxel and the        amount of the desired dose modification or typing a desired        modification to a dose quality metric).    -   Manipulation of graphical representations of dose distributions        and/or dose quality metrics via a graphical user interface.    -   Specifying a location on a graphical representation of the        subject using a mouse or similar computer pointing device and,        using a mouse button or keyboard input to indicate whether to        increase or decrease the dose at that location and/or to        indicate the magnitude of the desired dose modification.    -   Other computer input devices (trackball, touch screen, voice        command, video command and/or the like) may also be used

FIG. 7A shows an example of an operator communicating a desired dosemodification directly on a representation (e.g. a graphicalrepresentation) of a dose distribution 170. In the FIG. 7A example, theoperator selects a dose modification location (e.g. dose modificationvoxel) 171 inside a healthy tissue structure 152 and then communicates adesired dose reduction at that dose modification voxel 171.

FIG. 8A shows an example of an operator communicating a desired dosemodification on a representation (e.g. a graphical representation) of aDVH. In the FIG. 8A example, the operator selects a point 181 on the DVH182 corresponding to a target structure and indicates that an adjustmentcorresponding to a higher dose 183. As discussed above, block 220involves determining coordinates (e.g. voxel locations) and estimatedmagnitudes of desired dose modifications. Accordingly, block 220 mayinvolve a process for converting the DVH input of FIG. 8A tocorresponding dose modification coordinates/voxels and desired dosemodification magnitudes. Similarly, block 220 may involve process(es)for converting other input relating to other dose quality metric(s) tocorresponding dose modification coordinates/voxels and desired dosemodification magnitudes. In particular embodiments, the coordinates andmagnitudes of desired dose modifications may be determined in block 220by processes which comprise:

-   -   inverting the dose quality metric function, so that dose        magnitude and dose coordinates become function(s) of the dose        quality metric; and    -   calculating the required dose distribution modification        (magnitude and location) by applying the operator-indicated        modifications to the dose quality metric value in the inverted        dose metric function.

FIG. 9A shows part of the result of this block 220 inversion procedurewhich includes the dose modification coordinates (e.g. voxel locations)191 of the dose modifications corresponding to the FIG. 8A operatormanipulation of the DVH. In the illustrative example of FIG. 9A, theFIG. 8A DVH manipulation corresponds to desired increases in the dosemagnitude of coordinates (voxel locations) 191 inside target structure153. Although the magnitudes of the corresponding dose modifications arealso determined as part of the block 220 inversion procedure, they arenot explicitly shown in the schematic depiction of FIG. 9A.

FIG. 10 shows an example of an operator communicating a desired dosemodification on a representation (e.g. a graphical representation) ofanother type of dose quality metric (in the illustrated example, abiological index known as the Normal Tissue Complication Probability(NTCP) and Tumor Control Probability (TCP)). In the FIG. 10 example, theNTCP and TCP are displayed in the form of a bar histogram, the operatorselects NTCP 203 and indicates (at 201) that NTCP 203 should be reduced.As discussed above, when the operator input is a desired modification ina dose quality metric, block 220 may involve performing an inversionprocedure to determine the coordinates (e.g. voxel locations) andmagnitudes of the desired dose modifications corresponding to theoperator manipulation. The results of this block 220 inversion aredepicted in FIG. 11A which shows the coordinates (e.g. voxel locations)211 of the dose modification corresponding to the FIG. 10 operatormanipulation of the NTCP. In the illustrative example of FIG. 11A, theFIG. 10 NTCP manipulation corresponds to desired decreases in the dosemagnitude of coordinates (voxel locations) 211 inside healthy tissuestructure 152. Although the magnitudes of the corresponding dosemodifications are also determined as part of the block 220 inversionprocedure, they are not explicitly shown in the schematic depiction ofFIG. 11A.

In some embodiments, where desired dose modification input is receivedin the form of manipulation of dose quality metrics, techniques otherthan inversion may be used to predict desired dose modification voxelsand corresponding dose modification magnitudes. In one particularexample, a change to a DVH is received as input which comprises a changeto a point on a DVH curve which may be identified by a correspondingdose (D_selected) and a corresponding volume (V_selected). The dosemodification voxels may then be identified (in block 220) using a numberof techniques including: identifying voxels to be dose modificationvoxels if the voxels have values falling within D_selected+/−Δ, where Δmay be a fixed value (which may be operator-selectable), a fraction ofD_selected (which may be an operator-selectable fraction), a valuedetermined by calibration or empirical evidence and/or the like. If novoxels are identified to be dose modification voxels, then Δ may beexpanded and voxels may be re-identified until at least one dosemodification voxel is identified. If a large number of voxels (e.g. allvoxels for that structure or a number of voxels greater than a thresholdnumber or a threshold percentage of the voxels in a structure) areidentified to be dose modification voxels, then Δ may be reduced andvoxels may be re-identified. In some embodiments, all voxels inside thestructure for which the DVH is changed may be identified as dosemodification voxels. By way of non-limiting example, the magnitudes ofdose modifications may be determined on the basis of: a fraction of theD_selected value; a fraction of the maximum dose for the structure towhich the DVH corresponds; a fraction of a prescription dose assigned tothe structure to which the DVH corresponds; a fraction of the maximumprescription dose assigned to all structures; a fraction correlated with(e.g. proportional to) the amount of mouse or similar computer pointingdevice movement by an operator; a operator-selected quantity; a fixedquantity which may be an operator-configurable parameter or may be a“hard coded” constant; a combination of the above; and/or the like.

Block 220 involves determining the coordinates (e.g. voxel location(s))and magnitudes of desired dose changes. The coordinates determined inblock 220 to be associated with desired dose changes may be referred toas the desired dose modification coordinate(s)/voxel(s) and theassociated magnitudes may be referred to as the desired dosemodification magnitude(s). Typically, although not necessarily, suchdesired dose modification coordinate(s) and magnitude(s) are determinedon the basis of operator input, but could additionally or alternative begenerated based on other forms of input (e.g. computer-generatedautomated test input and/or the like). Such operator input may involvedirect specification of desired dose modification coordinates andmagnitudes or indirect specification of desired dose modificationcoordinates and magnitudes through specification of desired changes toone or more dose quality metrics. The examples shown in FIGS. 7A, 8A,9A, 10A and 11A are for illustrative purposes only and are not meant tolimit the scope of the invention. There are many other dose qualitymetrics that could be used. Furthermore, each dose quality metric couldbe represented in many different formats (graphical or otherwise). Theblock 220 procedure may involve the manipulation of any dose qualitymetric and representation that is a function of the dose distribution.

In some embodiments, block 220 may involve determining secondary dosemodification coordinates/voxels and corresponding dose modificationmagnitudes in addition to the primary dose modificationcoordinates/voxels and corresponding dose modification magnitudesdetermined in accordance with the techniques described above. Secondarydose modification voxels may be defined in a marginal region proximateto the primary dose modification voxels. By way of non-limiting example,such secondary dose modification voxels could be determined to be in amarginal region less than or equal to a threshold number of voxels awayfrom the primary dose modification coordinates. The threshold number ofvoxels that define the marginal region may be operator-configurable, maybe a system parameter which may be determined by one or more suitablecalibration procedures, may be a system parameter which may bedetermined based on empirical testing and/or data and/or the like.

The secondary dose modification magnitudes of the secondary dosemodification voxels may be less than the primary dose modificationmagnitudes of their corresponding primary dose modification voxels. Forexample, the secondary dose modification magnitudes may be a fraction aof the primary dose modification magnitudes (where 0<=a<=1). Thisfraction may be a function of the distance between a given secondarydose modification voxel and its corresponding primary dose modificationvoxel—e.g. within a marginal region of 3 voxels around a primary dosemodification voxel, the fraction a may be relatively high for thesecondary dose modification voxels that are nearest neighbors to theprimary dose modification voxel; lower for the secondary dosemodification voxels that are spaced by one voxel from the primary dosemodification voxel; and lowest for the secondary dose modificationvoxels that are spaced by two voxels from the primary dose modificationvoxel.

In other respects (e.g. for the purposes of other procedures involved inthe methods and systems described herein), secondary dose modificationvoxels determined as a part of block 220 may be treated, for the mostpart, in the same manner as primary dose modification voxels determinedin block 220. Accordingly, both primary dose modification voxels andsecondary dose modification voxels determined in block 220 may bereferred to simply as dose modification voxels.

Returning to FIG. 4B, method 18 then proceeds to block 221 whichinvolves determining, for each beam 159 in the block 42 beamconfiguration, the ray lines 163 that intersect the voxels correspondingto the block 220 desired dose modification coordinates. As discussedabove, each of these ray lines 163 is associated with a correspondingbeamlet 164 of a corresponding intensity distribution 165. Block 221 mayalso involve determining the coordinates of these beamlets 164. The raylines 163 that intersect the voxels corresponding to the block 220desired dose modification coordinates may be referred to as dose-changeray lines 163 and their corresponding beamlets 164 may be referred to asthe dose-change beamlets 164.

Method 18 then proceeds to block 223, which involves adjusting theintensities of the dose-change beamlets 164 identified in block 221. Forexample, if it is determined in block 220 that the dose corresponding toa particular desired dose modification voxel is to be decreased, thenblock 223 will typically involve decreasing intensities of thecorresponding dose-change beamlets 164. Conversely, if it is determinedin block 220 that the dose corresponding to a particular desired dosemodification voxel is to be increased, then block 223 will typicallyinvolve increasing intensities of the corresponding dose-change beamlets164.

Changes to the intensities of the dose-change beamlets 164 in block 223may be effected using a wide variety of techniques. By way ofnon-limiting example:

-   -   identical magnitude intensity changes or identical percentage        intensity changes may be applied to each dose-change beamlet        164;    -   identical intensity changes may be applied to one or more        subsets of dose-change beamlets 164. Such subsets of dose-change        beamlets 164 could correspond, for example, to consecutive        dose-change ray lines 163, to dose-change beamlets 164 from        every n^(th) (e.g. every second or third) beam 159, to randomly        selected dose-change beamlets 164 and/or the like;    -   different magnitude or percentage intensity changes may be        applied for all or a subset of dose-change beamlets 164; and/or    -   the like.

The magnitudes of the block 223 changes to the intensities of thedose-change beamlets 164 may be a function of (e.g. correlated with orproportional to) the block 220 desired dose modification magnitude(s).As discussed briefly above, initialization method 20 may optionallyinclude a procedure (block 47) which establishes an approximaterelationship between the intensities of beamlet(s) 164 having rayline(s) 163 that intersect a particular voxel (e.g. dose-change beamlets164 that intersect a dose modification voxel) and the corresponding dosedelivered to the particular voxel. While this approximate relationshipis shown as being determined in block 47 of the illustrated embodiment,this is not necessary and this approximate relationship may bedetermined as a part of one or more other procedures, including,possibly, separate procedures. This approximate relationship may be usedas a part of the block 223 determination of changes to the intensitiesof the dose-change beamlets 164. The approximate relationship betweenthe intensities of dose-change beamlets 164 and the magnitude of a dosechange to a dose modification voxel may have a form D=gni where D is thedose (or dose change) for the dose modification voxel, i is anapproximate intensity (or intensity change) value for a dose-changebeamlet 164, n represents the number of dose-change beamlets 164 for thedose modification voxel and g is a scaling variable. The scalingvariable g may be determined in block 47. Thus, for a particularmagnitude D of block 220 desired dose modification, the adjustments i tothe intensity values of the dose-change beamlets 164 may be determinedin accordance with this approximate relationship.

Restrictions may be applied to the block 223 intensity changes to thedose-change beamlets 164. Such restrictions may be related to practicalconsiderations—e.g. to more accurately reflect dose distributions whichare achievable in practice. By way of non-limiting example, suchintensity-change restrictions may include:

-   -   the intensities of the dose-change beamlets 164 (after the block        223 changes) must be greater than a minimum threshold (e.g.        negative intensities are not permitted);    -   the intensities of the dose-change beamlets 164 (after the block        223 changes) must be less than a maximum threshold;    -   the intensities of the dose-change beamlets 164 (after the block        223 changes) must be controlled such that spatial variations are        limited over the two-dimensional extent of a corresponding dose        distribution 165 or a dose distribution grid 162 (see FIG. 6).        For example, such a restriction may limit the maximum (magnitude        or percentage) change in intensity between immediately adjacent        (or some range of adjacent) beamlets 164 in a particular dose        distribution 165; and/or    -   the like.

If it is determined, in block 223, that a prospective intensity changeto one or more dose-change beamlets 164 would violate anintensity-change restriction, then a variety of strategies may beemployed in block 223 to overcome such a violation. By way ofnon-limiting example, such strategies may involve:

-   -   rejecting the block 220 desired dose modification;    -   adjusting the block 220 desired dose modification magnitude;    -   the one or more beams 159 corresponding to dose-change beamlets        164 resulting in intensity limit violations may be omitted from        subsequent dose estimation (discussed further below);    -   the intensity changes to one or more beamlets 164 associated        with secondary dose modification voxels may be omitted or the        marginal region of secondary dose modification voxels may be        reduced;    -   the magnitudes of one or more intensity changes applied to one        or more corresponding dose-change beamlets 164 may be modified        until the intensity-change restriction is no longer violated;    -   a combination of two or more of the above strategies; and/or    -   the like.        Once it is assured that no intensity-change restrictions are        violated by the prospective block 223 intensity changes, then        the intensities of the dose-change beamlets 164 are modified as        discussed above.

In some embodiments, block 221 may involve identifying secondarydose-change beamlets 164 and block 223 may involve adjusting theintensity values of secondary dose-change beamlets 164 in addition tothe identification and intensity value adjustment of the primarydose-change beamlets 164 in accordance with the techniques discussedabove. Secondary dose-change beamlets 164 may be identified in marginalregions proximate to the primary dose-change beamlets 164. By way ofnon-limiting example, such secondary dose-change beamlets 164 could beidentified to be in a marginal region less than or equal to a thresholdnumber of beamlets away from a primary dose-change beamlet. Thethreshold number of beamlets that define the marginal region may beoperator-configurable, may be a system parameter which may be determinedby one or more suitable calibration procedures, may be a systemparameter which may be determined based on empirical testing and/or dataand/or the like.

The block 223 intensity adjustments to the secondary dose-changebeamlets 164 may be less than corresponding adjustments to the primarydose-change beamlets 164. For example, the block 223 intensityadjustments to secondary dose-change beamlets 164 may be a fraction a ofthe intensity adjustments to the primary dose-change beamlets (where0<=a<=1). This fraction may be a function of the distance between agiven secondary dose-change beamlet and its corresponding primarydose-change beamlet—e.g. within a marginal region of 3 beamlets around aprimary dose-change beamlet, the fraction a may be relatively high forthe secondary dose-change beamlets that are nearest neighbors to theprimary dose-change beamlet; lower for the secondary dose-changebeamlets that are spaced by one beamlet from the primary dose-changebeamlet; and lowest for the secondary dose-change beamlets that arespaced by two beamlets from the primary dose-change beamlet.

In other respects (e.g. for the purposes of other procedures involved inthe methods and systems described herein), secondary dose-changebeamlets 164 may be treated, for the most part, in the same manner asprimary dose-change beamlets 164. Accordingly, both primary dose-changebeamlets and secondary dose-change beamlets may be referred to simply asdose-change beamlets.

Method 18 (FIG. 4B) then proceeds to block 224 which involvesdetermining changes in the achievable dose distribution based on theblock 223 changes to the intensities of the dose-change beamlets 164 andupdating the dose distribution accordingly. It will be appreciated thatmodifying the intensities of the dose-change beamlets 164 will not onlyimpact the estimated dose delivered to the desired dose modificationvoxels identified in block 220, but will also impact the estimated dosedelivered to other voxels (e.g. voxels in and around the paths of thedose-change ray lines 163). Typically, the maximum changes to theachievable dose distribution (caused by changes to the intensities ofthe dose-change beamlets 164) will occur in the desired dosemodification voxels and the changes to the achievable dose distributionwill be somewhat less in voxels surrounding the desired dosemodification voxels.

The block 224 estimation of the changes in the dose distribution mayinvolve the use of known dose estimation techniques such as, MonteCarlo, collapsed cone convolution, pencil beam, anisotropic analyticalalgorithm, Boltzman equation solvers and/or the like. The block 224estimation of dose distribution may involve one or more of the rapiddose distribution estimation techniques described herein. It isgenerally desirable that the block 224 dose estimation technique becomputationally efficient. Block 224 may involve using dose estimationtechniques that are able to update dose estimates resulting fromintensity changes to particular dose-change beamlets 164 alongindividual dose-change ray lines 163 which may be more computationallyefficient. The resulting changes in the dose estimates may then be added(or subtracted in the case of a dose reduction) to the existing dosedistribution estimate. In this regard, block 224 need only involveupdating the achievable dose distribution for the dose-change beamlets164 whose intensities were modified in block 223—i.e. it is notnecessary to recalculate the entire dose distribution estimate in block223. Typically, the number of dose-change beamlets 164 having theirintensities modified in block 223 will be a relatively small subset ofthe beamlets 164 associated with a given beam 159. In accordance withsome dose estimation techniques, the block 224 dose estimation updatemay therefore consume a relatively small amount of computationalresources compared to a full dose distribution estimate.

FIG. 4D depicts a dose-estimation update method 50 for determining thechanges in achievable dose distribution which may be used in block 224according to a particular embodiment. Dose-estimation update method 50of the illustrated embodiment assumes that a plurality of dosemodification voxels were specified in block 220 (e.g. the dosedistribution changes requested by an operator in block 220 resulted inmodifications to the dose at a plurality of coordinates/voxels).Dose-estimation update method 50 begins in block 51 which involves aninquiry into whether there are more dose-modification voxels to beconsidered in the dose-estimation update. In the first loop throughmethod 50, the block 51 inquiry will typically be positive (block 51 YESupdate path) and method 50 will proceed to block 52. Before proceedingto block 52, block 51 may also involve selecting one dose modificationvoxel to be the current dose modification voxel for this iteration ofthe method 50 dose-estimation update loop.

Block 52 of the illustrated embodiment involves identifying thedose-change beamlets 164 which correspond to the current dosemodification voxel. Such dose-change beamlets 164 may be thoseidentified in block 221 (FIG. 4B) as having corresponding dose-changeray lines 163 that intersect the current dose modification voxel. Foreach such dose-change beamlet 164, method 50 involves obtaining theintensity change for that beamlet 164 (in block 54) and estimating thedose contribution attributable to the intensity change for that beamlet164 (in block 56). The block 56 estimation of the dose contributionattributable to the intensity change for a particular dose-changebeamlet 164 may involve the use of known dose estimation techniques suchas, Monte Carlo, collapsed cone convolution, pencil beam, anisotropicanalytical algorithm, Boltzman equation solvers and/or the like. Theblock 56 dose estimation may additionally or alternative involve one ormore of the rapid dose distribution estimation techniques describedfurther below.

Method 50 of the illustrated embodiment then proceeds to block 58 whichinvolves summing the block 56 estimated dose contributions for all ofthe dose-change beamlets 164 corresponding to the current dosemodification voxel to obtain an estimated dose distribution update forthe current dose modification voxel. In block 60, the block 58 dosedistribution update for the current dose modification voxel mayoptionally be scaled to provide a scaled dose update grid correspondingto the current dose modification voxel. The term dose update grid may beused interchangeably with dose update distribution or dose modificationdistribution. As discussed above, an approximate relationship may beestablished (e.g. in block 47 of initialization method 20) between thedose change to a dose modification voxel and the corresponding intensitychanges to the dose-change beamlets 164 and, in accordance with thisapproximate relationship, changes to the intensities of the dose-changebeamlets 164 may be established in block 223. However, this relationshipis only approximate. Consequently, the block 58 sum of the dose changecontributions for each of the dose-change beamlets 164 may not yield thedesired magnitude (e.g. the block 220 desired magnitude) of dose changeto the dose modification voxel. In such cases, the block 58 sum of thedose change contributions for each of the dose-change beamlets 164 maybe scaled in block 60 to obtain a scaled dose update grid which achievesthe desired magnitude of dose change (e.g. the block 220 desired dosechange magnitude). The block 60 scaling of the dose update grid may alsobe accompanied by corresponding scaling to the intensities of thedose-change beamlets. The dose-change beamlets may be scaled by asimilar factor. For example, if the block 60 scaling of the dose changegrid involves a scaling factor s, then the intensities of thedose-change beamlets may be scaled by the same scaling factor s.

Since there may be an approximate relationship established between thedose change to the dose modification voxel and the correspondingintensity changes to the dose-change beamlets 164, the block 60 scalingmay be minimal. In some embodiments, block 60 scaling is not used. Insome instances, even where block 60 scaling is used, it may be desirableto limit the amount of block 60 scaling. For example, it may beundesirable to scale in a manner which may result in one or more beamletintensities that violate beam restrictions, such as any of the beamrestrictions discussed above. In some cases (e.g. because scaling is notused or is limited in amount), it may not be possible to achieve thedesired dose change magnitude (e.g. the block 220 dose modificationmagnitude) in the dose modification voxel. This circumstance ispermissible.

FIG. 12 schematically depicts an example of a scaled dose update grid234 corresponding to a particular dose modification voxel 231 accordingto a particular embodiment. In the FIG. 12 depiction, the current dosemodification coordinate is voxel 231 in target tissue structure 153.Referring to FIGS. 4B, 4D and 12, block 221 identifies the illustratedray lines 163 (and corresponding beamlets 164) for a series of beams 159to be the dose-change ray lines 163 and dose-change beamlets 164. Thechanges to the intensity values of the corresponding dose-changebeamlets 163 (determined in block 223 of FIG. 4B) are obtained in eachiteration of block 54 (FIG. 4D) and their respective dose distributioncontributions are estimated in each iteration of block 56 (FIG. 4D).These block 56 dose distribution contributions are summed in block 58and optionally scaled in block 60 to obtain scaled dose update grid 234illustrated in FIG. 12.

FIG. 12 shows a dose-update grid 234 comprising dose update values. Thedose update values determined for particular voxels in grid 234 arerepresented by the numerical values shown in the boxes of dose-updategrid 234. The dose update values for grid 234 are expressed in terms ofscaled dose update values—i.e. the dose update value of 100% at thecurrent dose modification voxel 231 represents a dose update of 100% ofthe desired dose change magnitude (e.g. the block 220 desired dosechange magnitude) and the dose update values of the other voxels aroundcurrent dose modification voxel 231 represent lower percentages of thedesired dose change magnitude. FIG. 12 shows that the maximum dosedistribution change occurs at the current dose modification voxel 231but that dose distribution changes also occur to a lesser extent insurrounding voxels. It will be appreciated that dose-update grid 234shown in FIG. 12 is a two-dimensional representation, but that inpractice the dose-update grid determined in accordance with method 50will be three-dimensional.

The block 60 dose-update grid 234 may represent an amount of dose to addto (or subtract from) an overall achievable dose distribution in block64. As discussed above, an initial overall achievable dose distributionmay be determined in block 46 (FIG. 4C). The block 46 initial estimateof the overall dose distribution may be updated in one or more previousiterations of method 18 (FIG. 4B). Block 64 may involve adding the doseupdate values of dose-update grid 234 to the overall dose distributionestimate. The overall dose distribution estimate will then be updatedwith the dose distribution contribution for the current dosemodification voxel 231. Method 50 then loops back to block 51 todetermine whether there are other dose modification voxels to beconsidered in the method 50 dose-estimation update. After one or moreloops through blocks 52-64, the block 51 inquiry will be negative,terminating method 50.

It will be appreciated by those skilled in the art that dose-estimationupdate method 50 of the FIG. 4D embodiment represents one particularmethod of updating dose estimates as a part of block 223 (FIG. 4B). Inother embodiments, equivalent dose-estimation updates could bedetermined using different orders of operations. By way of non-limitingexample, rather than looping through dose modification voxels anddose-change beamlets, the same or similar dose-estimation update resultscould be obtained by identifying all dose modification voxels, summingthe intensity changes to the dose-change beamlets resulting from all ofthe dose modification voxels and then estimating the dose changescorresponding to all of the dose-change beamlets in a single doseestimation process. Other orders of operations are conceivable forestimating dose updates as a part of block 224 (FIG. 4B). In someembodiments, the scaling and multiplication operations of blocks 60 and62 are not required as the magnitude of the desired dose change for aparticular dose modification voxel (see block 220 of FIG. 4B) mayalready be taken into account in the amount of the intensity changes tothe dose-change beamlets 164. In some embodiments, where all dosemodification voxels are simultaneously updated, scaling may occur atsome level that is a combination (e.g. some type of average) of thedesired scaling for all of the dose modification voxels.

Method 50 of the illustrated embodiment involves obtaining individualintensity changes to dose-change beamlets (in block 54), estimating dosechanges (in blocks 56, 58, 60, 62) and then adding (or subtracting) dosechanges to the existing dose distribution (in block 62) to obtain theblock 224 (FIG. 4B) updated dose distribution. This illustratedembodiment works with changes to intensities and doses and is possiblebecause many dose estimation techniques obey the principal ofsuperposition. In other embodiments, dose-estimation update methodswhich may be used in block 224 of method 18 (FIG. 4B) may involvediscarding an existing dose distribution (or part(s) thereof) and thenestimating a replacement dose distribution (or replacement part(s)thereof). Such replacement dose distributions (or replacement part(s)thereof) may be based on the absolute values of the adjusted intensitiesof the dose-change beamlets 164 (i.e. rather than the changes to theintensities of the dose change beamlets 164).

In one example of such an embodiment, the parts of an existing dosedistribution which could be discarded comprise the parts of the existingdose distribution contributed by the previous values of dose-changebeamlets 164, in which case the estimated replacement parts of theupdated dose distribution estimate would be the dose contributions fromthe new intensity values of the dose-change beamlets 164. In anotherexample of such an embodiment, the parts of an existing dosedistribution which could be discarded comprise the parts of the existingdose distribution contributed by the intensity distributions 165 ofbeams 159 (e.g. intensity distributions 165 having one or moredose-change beamlets 164), in which case the replacement parts of theupdated dose distribution estimate would be the dose contributions fromthe modified intensity distributions 165 of beams 159 (e.g. intensitydistributions 165 modified by updated intensity values for one or moredose-change beamlets 164). In another example of such an embodiment, theentire existing dose distribution could be discarded and a replacementdose distribution could be estimated based on dose contributions fromall of the updated intensity distributions 165 of all of the beams 159.These techniques of discarding parts of existing dose distributions andestimating replacement parts for the updated dose distribution estimatemay be particularly useful where they are used in conjunction with theconvolution technique for rapid estimation of achievable dosedistribution which is discussed further below.

At the conclusion of method 50 and/or block 224 (FIG. 4B), theachievable dose distribution has been updated to accommodate the desiredblock 220 dose distribution changes (e.g. operator-requested dosedistribution changes). Those skilled in the art will appreciate from thediscussion above, that there are a variety of techniques in which toupdate the achievable dose distribution in block 224. While some suchtechniques have been discussed above, there may still be other suitabletechniques which may be modifications of those discussed above or whichmay be different from those discussed above. Nevertheless, at theconclusion of block 224, the achievable dose distribution has beenupdated to accommodate the desired block 220 dose distribution changes.The updated estimate of the dose distribution at the conclusion of block224 may be displayed for the operator. Returning to FIG. 4B, method 18may optionally proceed to block 225 where one or more dose qualitymetrics may be updated on the basis of the block 224 updated dosedistribution. Such dose quality metrics may also be displayed for theoperator.

FIG. 7B shows a cross-section of the updated dose distribution estimate173 (determined in block 224) as a result of the FIG. 7A desired dosechange obtained or otherwise determined in block 220. Recalling that theFIG. 7A dose change corresponded to a desired reduction in the dosedelivered to voxel 171 of healthy tissue structure 152, FIG. 7B showsthat the maximum dose reduction occurs at voxel 171. However, updateddose distribution estimate 173 of FIG. 7B also shows that the doseestimate was reduced for voxels surrounding voxel 171. The updated dosedistribution shown in FIG. 7B may be displayed to an operator in block224.

FIG. 9B shows a cross-section of the updated dose distribution estimate193 (determined in block 224) as a result of the FIG. 9A desired dosechange determined in block 220. As discussed above, the FIG. 9A desireddose change corresponds to a desired change in the FIG. 8A DVH whichinvolves an increase in the dose delivered to target tissue structure153 and corresponding increases to the dose delivered to dosemodification voxels 191. FIG. 9B shows that the maximum dose increasesoccur at dose modification voxels 191, but that dose increases alsooccur for voxels surrounding voxels 191. The updated dose distributionshown in FIG. 9B may be displayed to an operator in block 224. FIG. 8Bshows the updated DVHs corresponding to the updated dose distributionestimate of FIG. 9B. The FIG. 8B DVHs may be determined and displayed toan operator in block 225. FIG. 8B shows that the target tissue DVH 182changes most near the desired change point 181, but that smaller changesalso occur to healthy tissue DVH 186.

FIG. 11B shows a cross-section of the updated dose distribution estimate213 (determined in block 224) as a result of the FIG. 11A desired dosechange determined in block 220. As discussed above, the FIG. 11A desireddose change corresponds to a desired change in the FIG. 10 NTCPbiological index which involves a decrease in the dose delivered tohealthy tissue structure 152 and corresponding decreases to the dosedelivered to dose modification voxels 211. FIG. 11B shows that themaximum dose decreases occur at dose modification voxels 211, but thatdose decreases also occur for voxels surrounding voxels 211. The updateddose distribution shown in FIG. 11B may be displayed to an operator inblock 224. Although not expressly shown in the drawings, updatedbiological indices may be determined and displayed to an operator inblock 225.

In some embodiments, method 18 and/or portions thereof may be performedin loops. For example, at the conclusion of blocks 224 and/or 225,method 18 may loop back to block 220 to permit additional dose changes(e.g. operator input of additional desired dose changes). In someembodiments, dose estimation updates (block 224) and/or updates to dosequality metrics (block 225) may be performed and/or displayedperiodically. The periods between such computation and/or displayupdates (which need not be temporal periods) may be defined using avariety of techniques. By way of non-limiting example, updates may beperformed:

-   -   each time that a block 220 desired dose modification is        requested or otherwise determined;    -   after multiple block 220 desired dose modifications are        requested or otherwise determined;    -   after a time interval;    -   if several block 220 desired dose modifications are requested,        it may be desirable to display a result which includes some        subset of the requested dose modifications;    -   after an achievable dose distribution and/or dose quality metric        has changed by a threshold amount;    -   a combination of the above (e.g. after a time interval or a        threshold number of desired dose modifications are requested);        and/or    -   the like.

Some of the procedures of method 18 may overlap with one another. Forexample, an operator may request multiple desired dose modifications(block 220) prior to the completion of the remainder of method 18. Asdesired dose modifications are communicated by the operator (orotherwise obtained in block 220), the rest of method 18 may be carriedout, so that modifications may be continuously applied and theachievable dose distribution may be continuously updated. It may occurthat one or more further desired dose modifications are requested priorto completion of the rest of method 18 for a previous desired dosemodification update. Further desired dose modifications may be places ina queue so that, once method 18 is completed for a particular desireddose modification, method 18 may be completed for the next desired dosemodification in the queue. In this way all desired dose modificationrequest changes will eventually be processed. In other embodiments,further desired dose modification requests may only be permitted aftermethod 18 has completed for a previous desired dose modificationrequest. Additional example schemes for addressing further desired dosemodification requests while method 18 is being carried out for previousdesired dose modification requests include, but are not limited to,rejection of every 2nd, 3rd or N^(th) request (where N is an integer)while the remaining requests are placed in a queue.

During method 18 (e.g. as a part of block 224 and/or method 50 (FIG.4D)), it may be desirable to prohibit or restrict certain desired dosemodification requests (e.g. block 220 desired dose modificationrequests). For example, reducing dose to target tissue structures 153below a threshold or increasing dose to healthy tissue structures 152above a threshold may be considered undesirable. Such thresholds maycomprise operator-specified thresholds, system threshold parametersand/or the like, for example.

Restrictions (e.g. thresholds) may be specified for the dosedistribution estimate itself and/or for one or more dose qualitymetrics. As part of method 18, proposed updates to the achievable dosedistribution and/or proposed updates to one or more dose quality metricsmay be evaluated with respect to one or more such restrictions. In theevent that such a restriction is violated, a variety of actions may betaken. By way of non-limiting example:

-   -   the block 220 desired dose modification request corresponding to        the restriction violation may be rejected;    -   the magnitude of the block 220 desired dose modification request        may be adjusted so that the restriction is no longer violated;    -   one or more additional changes to the block 220 desired dose        modification request may be made in attempt to overcome the        violation of the restriction; and/or    -   the like.

In the event that one or more additional changes to the block 220desired dose modification request are changes in attempt to overcomeviolation of the restriction, the following exemplary procedure may beused:

-   -   restriction violating coordinates (e.g. voxels) corresponding to        the voxels in the dose distribution that violate the restriction        may be determined. Such restriction violating coordinates may be        determined in a manner similar to the determination of the block        220 dose modification coordinates (e.g. for dose quality        metrics).    -   dose modifications may be applied to the restriction violating        coordinates and a resulting dose distribution estimates may be        obtained in accordance with method 18 of FIG. 4B.    -   after the new dose distribution estimates are calculated for the        changes to the restriction violating coordinates, the new dose        distribution estimates may be evaluated for restriction        violations.    -   If one or more restrictions remains violated, then the procedure        can be repeated until there are no longer restriction        violations.

At the conclusion of method 18 (any loops or any portions thereof),method 18 yields an achievable dose distribution and/or an estimateddose quality metric. Preferably, such achievable dose distributionand/or estimated dose quality metric will meet the operator's treatmentobjectives. The achievable dose distribution and/or dose quality metricsmay be output for use by another method or system. Such methods orsystems may comprise, for example, a computerized database, a treatmentplan optimization system, a radiation delivery apparatus and/or as aninput to any other system or device used in radiation treatment. Thecorresponding beamlet intensities and/or dose restrictions associatedwith the FIG. 18 dose distribution estimation may also be output for useby any such method or system.

By way of non-limiting example, as discussed above, method 18 of FIG. 4Bmay comprise a method for implementing the block 142 generation andmanipulation of achievable dose distribution as a part of radiationdelivery method 16 (FIG. 4A). In such an embodiment, the block 224 dosedistribution estimates and the corresponding beamlet intensities may beused in block 143 of radiation delivery method 18 to perform aniterative optimization process or the like to derive radiation deliveryparameters (e.g. beam configuration parameters and/or beam deliveryparameters). If iterative optimization is used in block 143, the doseestimation process involved in such optimization may (but notnecessarily) be the same as the dose estimation process involved in thedose generation and manipulation procedure of block 142 (e.g. in block46 of method 20 and block 56 of method 50). For example, in someembodiments, the dose estimation procedures used in dose generation andmanipulation block 142 may comprise one or more of the rapid doseestimation techniques described in more detail below; however, the block143 iterative optimization may involve one or more traditional methodsof dose estimation (e.g. Monte Carlo, collapsed cone convolution, pencilbeam, anisotropic analytical algorithm, Boltzman equation solvers and/orthe like) which may be more accurate for determining radiation deliveryparameters.

If iterative optimization is used in block 143, one or more outputs fromthe block 142 (method 18) generation and manipulation of estimated dosemay be used to aid in the derivation of the block 143 radiation deliveryparameters. By way of non-limiting example:

-   -   the block 224 achievable dose distribution and/or block 225        estimated dose quality metric(s) may be used in block 143 to        define the optimization objectives (e.g. cost function or the        like) of the optimization process;    -   the beamlet intensities determined in block 223 and        corresponding to the final block 224 achievable dose        distribution may be used to determine the beam intensity        required of the radiation delivery apparatus;    -   other metrics derived from the block 224 achievable dose        distribution may be used to define optimization objectives (e.g.        a cost function or the like) of the block 143 optimization        process; and/or    -   the like.

Block 143 does not necessarily require the performance of anoptimization process. In some embodiments, the output(s) of the block142 generation and manipulation of achievable dose distributions (e.g.block 224 achievable dose distributions, block 225 dose quality metricsand/or block 223 beamlet intensities) may lead be convertible directlyto radiation delivery parameters of sufficient accuracy. Such directderivation of radiation delivery parameters (i.e. without iterativeoptimization) in block 143 may occur, for example, where the block 224achievable dose distributions are calculated according to a sufficientlyaccurate estimation technique and various restrictions (e.g. on beamletintensities and/or dose estimates) are sufficiently robust.

Radiation treatment method 16 may then proceed to block 144, where theblock 143 radiation delivery parameters may be transferred to aradiation delivery apparatus. In block 145, a controller associated withthe radiation delivery apparatus (equipped with the radiation deliveryparameters) may then cause the radiation delivery apparatus to deliverradiation to the subject. The radiation received by the subject ispreferably similar to the achievable dose distribution output predictedin blocks 142 (FIG. 4A) and/or 224 (FIG. 4B).

Systems and methods according to various embodiments described hereininvolve estimating dose distributions based on one or more beamletintensities. Non-limiting examples of estimating dose distributionsinclude: the block 218 initialization procedure of method 18 (FIG. 4B)and the corresponding estimate of the initial dose distribution in block46 of initialization method 20 (FIG. 4C); the block 224 dose-estimationupdate procedure of method 18 (FIG. 4B) and the corresponding estimationat block 56 (FIG. 4D); and any dose distribution estimation that maytake place in the block 143 procedure for deriving radiation deliveryparameters (e.g. during iterative optimization). As discussed above,there are a variety of known techniques (e.g. Monte Carlo, collapsedcone convolution, pencil beam, anisotropic analytical algorithm,Boltzman equation solvers and/or the like) for estimating dosedistribution based on beamlet intensities. Any such techniques could beused in any of the intensity distribution estimation proceduresdescribed herein, although it may be preferable that one technique isused consistently throughout block 142 and one technique is usedconsistently throughout block 143 of radiation treatment method 16.

One aspect of the invention provides different methods for estimation ofachievable dose distributions. Such methods may be used to perform thedose distribution estimation procedures in any of the other methods andsystems described herein. In some embodiments, methods for estimatingachievable dose distributions are provided which are relatively rapid incomparison to currently available dose estimation techniques, such asMonte Carlo, collapsed cone convolution, pencil beam, anisotropicanalytical algorithm, Boltzman equation solvers and/or the like. Dosedistributions estimated in accordance with the inventive methodsdescribed herein may be referred to as rapid dose distribution estimatesto contrast them with traditional dose distribution estimates obtainedusing known techniques. Methods of estimating achievable dosedistributions according to various embodiments of the invention mayinvolve simplifications based on ray lines 163 (and correspondingbeamlets 164 of intensity distributions 165) emanating from radiationsource 161 and knowledge of how such ray lines 163 interact withcalculation grids which are used to map three-dimensional space insubject 160 (see FIG. 6). By way of non-limiting example, suchsimplifications may involve:

-   -   using simplified models of radiation scatter and/or radiation        transport as compared to traditional dose distribution        estimation techniques;    -   omitting the effects of inhomogeneous subject density;    -   omitting attenuation of beams 159 as a function of depth in        subject 160;    -   ignoring the distance from the radiation source to the subject        160;    -   a combination of the above; and/or    -   the like.

Given a set of beams 159 with known intensity distributions 165, rapidestimates of achievable dose distributions (and corresponding dosequality metrics) determined in accordance with some of the inventivemethods described herein may not yield the same achievable dosedistributions (and corresponding dose quality metrics) as traditionaldose estimation methods. However, where suitable limits are imposed onbeams 159, corresponding intensity distributions 165 and the intensitiesof individual beamlets 164, rapid dose distribution estimationtechniques described herein may yield dose distribution estimates thatare reasonably close to those that are physically deliverable. Suitableexamples of limitations on beams 159, corresponding intensitydistributions 165 and the intensities of individual beamlets 164 aredescribed above. In some embodiments, where rapid estimation ofachievable dose distributions are used during the process of treatmentplanning and/or delivery (e.g. method 16 of FIG. 4A), iterativeoptimization procedures may be used (e.g. in block 143 of method 16) todetermine radiation delivery parameters (e.g. physical systemparameters) capable of delivering the desired fast dose distributionestimates.

FIG. 13 is a schematic illustration of a method 70 for rapid estimationof achievable dose distribution according to a particular embodiment. Asdiscussed in more detail below, method 70 for rapid estimation ofachievable dose distributions involves, for each beam 159 in a beamconfiguration, convolving the two-dimensional intensity distribution 165i(x,y) associated with the beam 159 with a two-dimensional dose estimatekernel k(x,y) to obtain a convolved intensity distribution and, for eachconvolved beamlet in the convolved intensity distribution, projectingthe convolved intensity value along the ray line 163 associated with theconvolved beamlet. Estimating achievable dose distributions using a doseestimate kernel k(x,y) in accordance with method 70 may be an efficientway of estimating an achievable dose distribution based on an intensitydistribution.

Rapid dose distribution estimation method 70 commences in block 71 whichinvolves an inquiry into whether there are more beams to be consideredin the rapid dose distribution estimation. In the first loop throughmethod 70, the block 71 inquiry will typically be positive (block 71 YESupdate path) and method 70 will proceed to block 72. Before proceedingto block 72, block 71 may also involve selecting one beam to be thecurrent beam for this iteration of the method 70 rapid dose distributionestimation loop. In block 72, method 70 involves performing aconvolution operation which comprises convolving the two-dimensionalintensity distribution i(x,y) associated with the current beam with atwo-dimensional dose estimate kernel k(x,y) to obtain a two-dimensionalconvolved intensity distribution f(x,y). The coordinates x,y may bedefined in the plane of grid 162 of the intensity distribution 165 (seeFIG. 6). The resultant convolved intensity distribution f(x,y) may bedefined for, or otherwise mapped to, the coordinates associated with thebeamlets 164 of the current beam which may, in the context of theconvolved intensity distribution f(x,y), be referred to as convolvedbeamlets 164. As part of block 72, each convolved beamlet 164 isassociated with a corresponding ray line 163 and a correspondingconvolved intensity value.

The dose estimate kernel k(x,y) may be intended to approximate theamount of radiation scatter and energy transport resulting fromradiation interacting with tissue. In some embodiments, the doseestimation kernel k(x,y) comprises a point spread function.

In some embodiments, the dose estimation kernel k(x,y) comprises alinear combination of a plurality of point spread functions. In oneexemplary embodiment, the dose estimate kernel k(x,y) comprises a linearcombination of one or more 2-dimensional Gaussian functions:

k(x,y)=A ₁e^(−(x) ³ ^(−y) ² ^()/σ) ¹ ² +A ₂e^(−(x) ² ^(−y) ² ^()/σ) ²² + . . . +A _(n)e^(−(x) ³ ^(−y) ² ^()/σ) ^(n) ²   (1)

where A_(i) are magnitude variables of the various Gaussian functionsand σ_(i) are variables representative of the radial spread of thevarious Gaussian functions. The variables A_(i) and σ_(i) may beoperator-configurable, may be system parameters which may be determinedby one or more suitable calibration procedures, may be system parameterswhich may be determined based on empirical testing and/or data and/orthe like. The variables A_(i) and σ_(i) may depend on the type ofradiation. It will be appreciated by those skilled in the art that theequation (1) point spread function is merely an example point spreadfunction and that dose estimation kernel k(x,y) may comprise a varietyof other point spread functions and/or linear combinations of pointspread functions. In some embodiments, the dose estimation kernel k(x,y)(or one or more parameters thereof) may be experimentally determined(e.g. from calibration type measurements and/or the like). In someembodiments, the dose estimation kernel k(x,y) (and/or its parameters)may be stored in accessible memory (e.g. in a look up table or thelike).

Convolution operations can be computationally intensive and can consumerelatively large amounts of processing resources. To reduce this burdenon computational resources, the block 72 convolution may involveconverting the two-dimensional intensity distribution i(x,y) and thetwo-dimensional dose estimate kernel k(x,y) to the Fourier domain.Advantageously, a convolution operation in the spatial domain may beimplemented as a multiplication operation in the Fourier domain. Thetwo-dimensional intensity distribution i(x,y) and the two-dimensionaldose estimate kernel k(x,y) may be converted to the Fourier domain usingany of a wide variety of known computational techniques for performingFourier transforms (e.g. fast Fourier transforms (FFT) and/or the like).The convolved intensity distribution f(x,y) may therefore be calculatedaccording to:

f(x,y)=IFT[FT[i(x,y)]×FT[k(x,y)]]  (2)

where FT[] and IFT[] are respectively Fourier transform and inverseFourier transform operators. It will be appreciated that, in absence ofa change to the kernel function k(x,y), the Fourier transform of thekernel function FT[k(x,y)] need only be calculated once and the resultmay be stored (e.g. in a look up table in accessible memory and/or thelike).

Method 70 then proceeds to block 74 which involves a loop for eachconvolved beamlet 164 in the current beam 159. For each convolvedbeamlet 164 in the current beam 159: block 76 involves projecting theray line 163 corresponding to the convolved beamlet 164 into thecalculation grid and identifying voxels in the calculation grid whichare intersected by the ray line 163 and block 78 involves adding theconvolved intensity value for the convolved beamlet 164 to each voxelidentified in block 76. Method 70 then loops back to block 71 todetermine whether there are more beams to be considered in the method 70rapid dose estimation. After one or more loops through blocks 72-78, theblock 71 inquiry will be negative, terminating method 70.

Rapid dose distribution estimation method 70 involves the principal ofsuperposition. As discussed above in connection with dose estimationupdate method 50, dose estimation techniques which involve the principalof superposition may operate on changes (e.g. determining changes todose distributions that result from changes to beam and/or beamletintensities) or on absolute values (e.g. discarding dose contributionsfrom previous values of beam and/or beamlet intensities and estimatingnew dose contributions based on the new absolute values of the beamand/or beamlet intensities).

The above-described method 70 for rapid dose distribution estimation maybe augmented by incorporating an estimate for attenuation of radiationas it passes through the subject. For this purpose, in some embodiments,an additional attenuation function a(d) may be applied to account forsuch attenuation. Such an attenuation function a(d) may cause the block72 convolved intensity values to decrease with distance d along the raylines 163 which they are projected in block 76, so that their respectiveblock 78 dose contributions decrease with distance d along theirrespective ray lines 163. By way of non-limiting example, an attenuationfunction a(d) may be multiplied to the dose contribution values in block78 before such dose contribution values are added to each voxelintersected by ray lines 163. A variety of different decreasingattenuation functions a(d) are suitable to model this attenuation andthe choice of particular attenuation function a(d) may depend on thecharacteristics of the radiation. In one particular embodiment, anattenuation function a(d) may be provided by an exponential function ofthe form:

a(d)=Be^(−kd)  (3)

where B is a magnitude variable, k is a variable characterizes the rateof attenuation with depth and d represents the distance along aparticular ray line 163. In some embodiments, the variable d mayrepresent the depth of penetration into the body of the subject—i.e.there is negligible attenuation prior to the radiation impinging on thebody of the subject. The variables B and k may be operator-configurable,may be system parameters which may be determined by one or more suitablecalibration procedures, may be system parameters which may be determinedbased on empirical testing and/or data and/or the like. Like the Fouriertransform of the kernel function, the values of the attenuation factor(e.g. equation 3) may be pre-calculated and stored in a look up table orthe like.

In some embodiments, beam configurations are contemplated which involvea plurality of beams 159 at a corresponding variety of locations along atrajectory which involves a 360° rotation of the radiation source withrespect to the subject. In some embodiments, it is contemplated that theradiation source will move continuously with respect to the subjectabout the 360° trajectory. In such embodiments, the 360° trajectory canbe approximated by a plurality of sample beams. For the purpose of thisdescription, sample beams on a trajectory where it is contemplated thatthe radiation source will move continuously relative to the subject canbe treated in the same manner as discrete beams 159.

FIG. 14 schematically depicts a 360° trajectory 240, a plurality ofbeams 159 at angularly evenly spaced locations around trajectory 240 anda two-dimensional cross-section of a dose update grid 242 estimated tobe achievable by the plurality of beams 159. Beams 159 may be discretebeams or sample beams associated with a continuously moving radiationsource. The achievable dose update grid 242 (having voxel dosecontributions represented by the numbers in the boxes of the illustratedgrid) has been scaled to a value of 100 at the dose modification voxel241. The FIG. 14 dose update grid 242 may be obtained, for example, inaccordance with block 60 of method 50 (FIG. 4D). The FIG. 14 dose updategrid results from an equal intensity change to each of the beamletsassociated with the ray lines 163 that intersect dose modification voxel241.

FIG. 15 depicts an example profile 243 of the FIG. 14 achievable doseupdate grid 242 that intersects dose modification voxel 241. The peak ofthe dose change depicted in example profile 243 occurs at the locationof dose modification voxel 241 (x=0 in FIG. 15). Due to the 360°trajectory 240 and plurality of beams 159, the magnitude of the dosechanges in areas surrounding dose modification voxel 241 decreasesrapidly with distance from dose modification voxel 241. To achieve thisproperty (i.e. where relatively small changes occur to the dose atlocations away from particular dose modification voxels 241), it may bedesirable that there be a relatively large number of beams 159 in 360°trajectory 240. As discussed above, in some embodiments, the radiationsource moves continuously with respect to the subject and beams 159 areactually sample beams. In other embodiments, the angular separationbetween discrete beams 159 along the 360° trajectory 240 is less than20°. In some embodiments, this angular separation is less than 15°.

An additional property of the 360° trajectory 240 and the correspondingdose update grid 242 is that the same dose update grid may be translatedto any desired dose modification voxel. An example of thistranslatability is shown in FIG. 16 which depicts a dose update grid 244which is the same as dose update grid 242 (FIG. 14) except that doseupdate grid 244 of FIG. 16 has been translated to a different dosemodification voxel 245. The translatability of the dose update grid 242for the 360° trajectory 240 may be permitted because every voxel in theplane of motion of the radiation source along trajectory 240 has a full360° of ray lines which intersect the voxel and corresponding beamletswithin beams 159. Some embodiments may achieve computational efficiencyby determining the dose update grid 242 for a 360° trajectory 240 andstoring the dose update grid 242 in accessible memory or the like (e.g.in a look up table). In this manner, the dose update grid 242 for a 360°trajectory 240 may be recalled from memory each time that it is used.

A 360° trajectory 240 is used as an example for illustration purposes.Beam configurations with other trajectories (e.g. other angular rotationranges and/or other) motions may also be used. Furthermore, it may bedesirable to use different angular ranges of beams when permittingmanipulation of achievable dose (e.g. in block 142). For angular rangesof beams smaller than 360°, the corresponding angular range of ray lines163 intersecting a dose distribution coordinate (e.g. a dosemodification voxel) will be reduced. In some embodiments, dose updategrids for alternative motion ranges may also be pre-calculated andstored (e.g. in a look up table in an accessible memory) for subsequentretrieval. A library of dose update grids referred to as radialmodification dose (RMD) distributions may be stored in accessiblememory. Such a library of RMDs may include RMDs for N incremental motionranges from 0°-N°, for example, where N has incremental values goingfrom 0°-360°. Specific angular ranges of beams may be determined bysubtracting two dose modification distributions stored in the library.For example:

RMD(θ

φ)=RMD(0

φ)−RMD(0

θ)  (4)

Where θ

φ indicates an angular range of beams going from angle θ to angle φ.Using a subtraction operation like that of equation (4) reduces thenumber of actual RMDs that must be stored in memory. A graphical exampleis shown in FIGS. 18A, 18B, 18C, where RMD dose distributions aredisplayed as pixel map images, in which brighter pixels indicate higherdoses. FIG. 18A represents a RMD for the angular range 0°-90° and FIG.18B represents a RMD for 0°-45°. Both the FIGS. 18A and 18B RMDs may bestored in accessible memory. Assuming that it is desired to determine aRMD for the angular range 45°-90°, then the 0°-45° RMD (FIG. 18B) may besubtracted from the 0°-90° RMD (FIG. 18A) to yield the 45°-90° RMD shownin the representation of FIG. 18C.

FIG. 17 schematically illustrates a system 300 according to a particularembodiment of the invention. System 300 (or portions thereof) may beused to perform some or any of the methods described above. System 300comprises a radiation delivery apparatus 302 which may be similar to anyof the radiation delivery apparatus described herein. Operator 312 mayinteract with radiation delivery apparatus 302 via user interface 302Bwhich may include both hardware components and software components. Inthe illustrated embodiment, the operation of radiation deliveryapparatus 302 is controlled by a controller 302A. In the illustratedembodiment, controller 302A receives radiation delivery parameters froman external processor 304. Processor 304 may comprise any suitablecomputer or digital processing unit(s). Processor 304 may carry outcomputer readable software instructions. Processor 304 may be incommunication with radiation delivery apparatus 302 using any suitablecommunication hardware and/or software including network communicationhardware and/or software. An operator 312 may interact with processor304 using a suitable user interface 306 which may include both hardwarecomponents and software components.

Processor 304 of the illustrated embodiment has access to acomputer-readable memory 308 which may house software instructions 310.In other embodiments, processor 304 may obtain instructions 310 from oneor more other sources. When executed by processor 304, softwareinstructions 310 may cause processor 304 to perform one of more of themethods described herein (e.g. radiation delivery method 16 (FIG. 4A),method 18 for generation and manipulation of achievable dose (FIG. 4B),dose estimation update method 50 (FIG. 4D), rapid dose estimation 70(FIG. 13) and/or the like). In the illustrated embodiment, processor304, user interface 306 and memory 308 are part of a computer system314, although this is not necessary. In other embodiments, thesecomponents (or parts thereof) may be separately implemented.

In still other embodiments, one or more of the methods described hereinmay be performed by controller 302A (or some other suitable processor)that is part of radiation delivery apparatus 302. In such embodiments,radiation delivery apparatus 302 may comprise (or otherwise have accessto) suitable memory which may comprise suitable computer softwareinstructions.

EXAMPLES

The examples set out below represent non-limiting examples of methods,systems and various features of methods and systems according to variousembodiments. These non-limiting examples are for illustrative purposesonly and are not intended to represent limiting features unlessotherwise claimed below.

Pseudocode Example

Setup Initialization

-   -   Import subject image and segmented tissue structure information        (e.g. tumor target, healthy tissue structures (e.g. organs),        other tissue of interest, target prescription)    -   Select dose estimate kernel (e.g. point spread function (PSF))        based on beam energy and associated scattering characteristic(s)    -   Calculate Fast Fourier Transform (FFT) of PSF and store in        accessible memory for later use    -   Create voxel matrix (calculation grid) overlaid with image data        from subject including tissue structure information    -   Identify voxels located within any structure(s) of interest        -   identify voxels partially within a structure (e.g. at the            edge of the structure) and assign partial volume values            (e.g. in a range of 0-1) to those voxels for the purpose of            calculating dose quality metrics based on such voxels    -   Select beam configuration (e.g. number, location and direction        of beams)        -   Desired beam configuration may include a number of fixed            beams (e.g. 5 to 9 beams or other numbers of fixed beams)        -   If desired beam configuration involves continuously moving            beams, then a number of beam samples (e.g. 10 or more beam            samples) along the trajectory may be used to represent            dynamic source motion    -   Initialize beamlet intensities    -   Calculate estimated dose distribution resulting from initial        beamlet intensities    -   Calculate initial dose volume histogram (DVH) (and/or other        initial dose quality metric(s))    -   Display initial DVH(s) and/or initial dose distribution overlaid        with image data from subject including tissue structure        information        -   dose may be represented via cross sectional view(s) of the            image data            -   dose can be represented as a color wash            -   dose can be represented as an iso-line plot (line                contours of constant dose)            -   dose can be represented using any other suitable display                technique        -   three-dimensional dose display (so-called “dose cloud”            displays) could additionally or alternatively be used

Beamlet Initialization

-   -   Create two-dimensional beamlet matrix for each beam    -   For each target structure:        -   Target structure is projected onto the beamlet matrix        -   A margin may be added to the projection to ensure proper            coverage of the target structure by the resulting dose            distribution        -   Assign an intensity value to beamlets corresponding to            target structure.

Such intensity value may be correlated with (e.g. proportional to) theprescription dose for the target structure

-   -   Optional:        -   For target structures that overlap in a given beam            projection, weight the beamlet intensities in the            overlapping area with the overlapping target structure that            has the highest prescription dose; or        -   For target structures that overlap in a given beam            projection, weight the beamlet intensities in the            overlapping area with the overlapping target that has the            lowest prescription dose

Rapid Estimation of Achievable Dose Distribution

-   -   Estimate dose contribution—For each beam:        -   Convolve beamlet intensity matrix by the dose estimate            kernel (e.g. PSF)            -   Perform convolution by: determining the FFT of the                beamlet matrix; multiplying by the pre-calculated FFT of                the dose estimate kernel; and determining the Inverse                FFT of the result    -   Determine intersection of ray lines from beamlet matrix with        voxels—For each voxel where the dose has not been previously        determined:        -   For each beam:            -   Determine the location where any ray line passing                through the voxel intersects with the beamlet matrix            -   Store the beamlet intersection location in accessible                memory for use in subsequent dose calculations (so that                the beamlet intersection location only needs to be                determined once)                -   Achievable dose estimation may be limited to voxels                    of interest. For example:                -    For DVH calculation, achievable dose estimation may                    be limited to voxels within target and healthy                    tissue structure(s)                -    In the case where a dose plane cross section is                    being displayed, achievable dose estimation may be                    limited to voxels in that plane    -   Calculate total dose—For each voxel:        -   Extract the dose contribution—For each beam:            -   Extract the convolved intensity value from the convolved                intensity distribution at the location of the previously                determined beamlet matrix intersection        -   Sum the contribution from each beam

Permit Dose Volume Histogram Manipulation

-   Operator selects a point on a DVH curve of a particular structure    and requests a change of the curve shape at that point    -   Identify the dose and volume coordinate values of the selected        point (D_selected, V_selected)    -   The request may be communicated by selecting the DVH with a        mouse or similar computer pointing device click and then moving        the mouse or similar computer pointing device        -   movement left and/or down indicates may indicate a dose            reduction (desired dose change is negative)        -   movement right and/or up may indicate a dose increase            (desired dose change is positive)    -   Determining a magnitude of the desired dose change may involve,        for example:        -   A fraction of the D_selected value        -   A fraction of the maximum dose for that structure        -   A fraction of a prescription dose assigned to that structure        -   A fraction of the maximum prescription dose assigned to all            structures        -   A fraction correlated with (e.g. proportional to) the amount            of mouse or similar computer pointing device movement        -   A quantity set by the operator        -   A fixed quantity which may be an operator-configurable            parameter or may be a “hard coded” constant        -   A combination of the above-   For the selected structure, voxels having dose values close to    D_selected may be identified as dose modification voxels    -   Voxels may be identified as dose modification voxels if the        voxels have values falling within D_selected+/−Δ        -   Δ may be a fixed value (which may be operator-selectable) or            a fraction of D_selected (which may be an            operator-selectable fraction)    -   If no voxels are identified to be dose modification voxels then        Δ may be expanded and voxels may be re-identified        -   This process repeats until at least one voxel is identified            as a dose modification voxel    -   If a large number of voxels (e.g. all voxels for that structure        or a number of voxels greater than a threshold number or a        threshold percentage of the voxels in a structure) are        identified to be dose modification voxels, then A may be reduced        and voxels may be re-identified    -   In some embodiments, all voxels inside the structure for which        the DVH is changed may be identified as dose modification voxels-   Optional: identification of secondary dose modification voxels in    marginal region around primary dose modification voxels and    assignment of suitable magnitude of dose modification to secondary    dose modification voxels-   Dose modification is performed for voxels identified as dose    modification voxels (see Dose Modification below)-   Once Dose Modification is performed, DVH is re-calculated based on    new estimated dose-   Check whether any dose restrictions are violated (see Dose    Manipulation Under Dose Restrictions)-   Display is updated with new DVH

Dose Modification

-   For each voxel identified to be a dose modification voxel    (Vox_identified) and for each beam:    -   Determine the location(s) where ray line(s) passing through        Vox_identified intersect with the beamlet matrix    -   Modify intensity values of beamlet(s) at intersection point(s)        (dose-change beamlets) using a default quantity        -   The default quantity may be correlated with (e.g.            proportional to) the magnitude of the desired dose change            and may also depend on the number of dose-change beamlets            who ray lines intersect Vox_identified    -   Optional: identify and determine intensity value adjustment for        secondary dose-change beamlets in a marginal region around        primary dose-change beamlets-   Modified beamlets are evaluated for possible intensity restriction    violations. By way of non-limiting example:    -   Intensity values that are less than a minimum threshold        -   Corrected by increasing violating beamlet intensities to            minimum threshold    -   Intensity values greater than a maximum threshold        -   Corrected by decreasing violating beamlet intensities to            maximum threshold    -   Variations in intensity over the two dimensional extent of the        beamlet matrix may also be limited (e.g. a maximum variation of        a fixed percentage from one beamlet to an adjacent beamlet)        -   Corrected by increasing or decreasing the intensities of            modified beamlets so that variation restriction is no longer            violated-   Dose is estimated at voxels for all beams using Rapid Estimation of    Achievable Dose Distribution    -   Dose may be calculated for only a subset of voxels. For example:        -   Voxels of the selected structure only        -   Voxels of all structures        -   Voxels of all structures plus currently displayed cross            sectional plane-   Estimated dose for each dose modification voxel (Vox_identified) is    compared to dose requested by operator:    -   Determine difference between the mean estimated dose and mean        operator-requested dose for all dose modification voxels        Vox_identified    -   Rescale magnitude of intensity modification for all dose-change        beamlets is rescaled so that mean dose for each dose        modification voxel (Vox_identified) is equal to mean        operator-requested dose requested by operator unless the        rescaling of the dose-change beamlets results in a violation of        the beamlet intensity restrictions

Dose Manipulation Under Dose Restrictions

-   Restrictions on the shape of DVH curves (or other restrictions on    the dose distribution itself or on other dose quality metrics) may    be designated by the operator or may be otherwise incorporated into    the procedure (e.g. as global parameters of the system/method). For    example:-   No voxels within a structure can be below a specified dose threshold    -   No voxels within a structure can exceed a specified dose        threshold    -   A specified percentage of volume of a structure cannot exceed a        specified dose threshold    -   A specified percentage of volume of a structure cannot exceed a        specified dose threshold-   When a dose manipulation is performed (through DVH or otherwise) the    dose distribution is evaluated for potential dose restriction    violations-   Violations are detected by comparing the estimated dose distribution    and/or dose quality metrics (e.g. DVH) with the dose restrictions    -   Voxels contributing to the violation are identified    -   The magnitude of dose change required for each violating voxel        to satisfy the restriction is calculated    -   Perform Dose Modification (see above) using the violating voxels        and voxel dose change requirements as inputs    -   Repeat as necessary until there are no further dose restriction        violations

Example Application

The following non-limiting example is meant to provide furtherunderstanding of how various aspects and features of the invention couldbe used in practice. FIG. 19A is a three-dimensional rendering of atarget structure 281 and healthy tissue structure 282 and FIG. 19B is across-sectional view bisecting (and showing outlines of) targetstructure 281 and healthy tissue structure 282 along the plane 283. FIG.19B shows the x and y axes scales in millimeters.

The beam configuration used in this particular example comprises a 360°degree rotation of the radiation source with respect to the subject.Such a beam configuration could be implemented using the radiationdelivery apparatus of FIG. 1 or 2, for example. In this example, it isassume that the radiation source moves in the x-y plane of FIGS. 19A,19B. The initial estimated dose (e.g. block 46) is generated using 180beams distributed along the path of the radiation source. The initialestimate of the dose distribution is determined using initial intensitydistributions (e.g. block 44) wherein the initial beamlet intensitiesare proportional to the target prescription dose for ray lines thatproject through target structure 281 and zero otherwise. In thisexample, the target prescription dose is 60 Gy. The initial dose isestimated using the convolution based rapid dose estimation techniquedescribed above, with the dose estimate kernel according to equation (1)and using the inverse Fourier transform method of equation (2). At eachvoxel, the total estimated dose is the sum of dose contributions fromeach beam to that voxel. FIG. 20A shows a representation of across-section 291 of the initial estimated dose distribution for theFIG. 19A target tissue structure 281 and healthy tissue structure 282.FIG. 20B shows the DVH for the full three-dimensional target structure292 and healthy tissue structure 293. The FIG. 20A dose distribution 291is depicted as a grayscale pixel map, with lighter pixels indicatinghigher dose. The initial dose estimate 291 is fairly uniform in thevolume of target structure 281 with the healthy tissue structure 282receiving substantial dose in the region adjacent to target structure281.

Once the initial dose estimate is established, manipulation of theestimated dose distribution may be permitted (e.g. by an operator). Theoperator may desire to establish adequate volumetric coverage of targetstructure 281 with the prescription dose. This may be accomplished byincreasing the minimum dose to target tissue structure 281 throughmanipulation of the DVH. FIGS. 21A, 21B and 21C show an example ofincreasing the minimum dose to target structure 281 through DVHmanipulation. FIG. 21A shows a magnified portion 301 of the FIG. 19B DVHplot 292. The operator may select the DVH curve near a low dose point303 on the curve 301 (e.g. using the computer mouse or similar computerpointing device), depress the mouse button, and then translate curve 301to the left (towards lower dose) or to the right (towards higher dose).In this example, the operator increases the dose by moving the selectedpoint 303 on DVH curve 301 to the right as shown at 304. When theoperator moves the DVH curve in this manner, the dose modificationvoxels (and corresponding dose modification magnitudes) are determinedand a dose modification is applied to those dose modification voxels. Inthis example, the FIG. 21A manipulation corresponds to three dosemodification voxels. When the dose modification is applied to thesethree dose modification, voxels it is determined that no intensitylimits will be violated. FIG. 21B shows examples of three dosemodification distributions 305 resulting from the FIG. 21A dosemodification request communicated by the operator (i.e. from the threedose modification voxels). In the FIG. 21B representations, lightergrayscale indicates higher dose. It may be observed that eachmodification 305 is well localized to specific areas of the dosedistribution. FIG. 21C shows an updated dose distribution andcorrespondingly updated DVHs for the target structure 307 and healthytissue structure 308. The updated target structure DVH 307 of FIG. 21Cshows that the minimum dose to the target structure 281 is higher thanit was preceding the modification (see DVH 292 of FIG. 20B). Also, itmay be observed that healthy tissue DVH 308 has not changedsubstantially (compare to healthy tissue structure DVH 293 of FIG. 20B),which is a result of the changes being localized to target structure 281during dose modification.

Now that the operator has established an acceptable dose distributionfor target structure 281, it may be desirable to place restrictions onDVH manipulation so that the acceptable dose distribution is maintainedduring further dose modification. For example, such a restriction couldbe that 100% of the target structure 281 should receive 57 Gy and 0% ofthe target structure 281 should receive more than 63 Gy. The operatormay then proceed with modifying the DVH 315 corresponding to healthytissue structure 282 by selecting a point on DVH 315 and dragging themouse or similar computer pointing device to the left 317 (for dosereduction). Once the dose modification voxels corresponding to thisdesired DVH modification have been determined, a dose modification isapplied to each dose modification voxel. In this case restrictions onthe intensity changes necessitate the use of a smaller number ofbeamlets. FIG. 22B shows corresponding dose modification distributions318 which may be different from those of FIG. 21B due to the smallernumber of beamlets used. Note that the dose modification distributions318 are well localized inside the healthy tissue structure 282. FIG. 22Cshows the updated DVH 319. FIG. 22C shows that the dose to healthytissue structure 282 has been reduced as desired.

With the healthy tissue dose reduction illustrated in FIG. 22C, therestriction 321 placed on the minimum dose for target tissue structure281 is violated (see FIG. 22C). A corrective dose modification may beautomatically applied to bring the target structure DVH back within theconstraint 321. The dose modification voxels where the dose distributioncauses the violation of the DVH constraint 321 are determined and dosemodifications are applied at those dose modification voxels. FIG. 23Ashows two example dose modification distributions 323 used to correctthe violation of constraint 321 on the target dose distribution. FIG.23A shows that in this case the dose modification is applied at the edgeof target structure 281 close to healthy tissue structure 282 where theFIG. 22 dose decrease was applied. Again the dose modificationdistributions are well localized so that areas surrounding the dosemodification voxels are not substantially impacted. FIG. 23B showstarget structure DVH 324 after application of the FIG. 23A dosemodification 323 and how target structure DVH 324 is now within therestrictions (321 and 314). The healthy tissue structure DVH 325 haschanged only slightly from that of FIG. 22C due to the dose changesbeing localized primarily within the target structure 281. FIG. 23Cshows a representation of the resultant cross-sectional dosedistribution 326 which shows a reduction in dose to the healthy tissuestructure compared to that of FIG. 21C, as was originally desired by theoperator.

Further dose modifications may be imposed by the operator by repeatingin a similar fashion the process described above. For example, furtherreductions in the healthy tissue structure dose may be applied under theconstraints 321 and 314 (FIG. 23B). Eventually an equilibrium will bereached where further reduction in healthy tissue structure dose cannotbe achieved without violating the restrictions on the target dose. FIG.24A shows the DVH for the target 331 and healthy tissue structure 332 atthe end result of a series of dose modifications by the operator. FIG.24B shows the corresponding cross-sectional estimated dose distribution333 corresponding to these modifications. The DVH 332 and estimatedcross-sectional dose distribution 333 for the healthy tissue structure282 have been reduced considerably as compare to the initial DVH 293(FIG. 20B) and dose distribution 291 (FIG. 20A). A high uniform dose ismaintained in the target as seen in the final target DVH 331 (FIG. 24A)and cross-sectional dose distribution 333 (FIG. 24B).

After the dose manipulation is complete the radiation deliveryparameters for the beam configuration may be determined. The radiationdelivery parameters may then be transferred to the control system andcomputer of the radiation delivery apparatus. The radiation may then bedelivered to the subject, thereby delivering a dose distribution in thesubject substantially similar to that derived from the dosemanipulation.

Embodiments of the present invention include various operations, whichare described herein. These operations may be performed by hardwarecomponents, software, firmware, or a combination thereof.

Certain embodiments may be implemented as a computer program productthat may include instructions stored on a machine-readable medium. Theseinstructions may be used to program a general-purpose or special-purposeprocessor to perform the described operations. A machine-readable mediumincludes any mechanism for storing information in a form (e.g.,software, processing application) readable by a machine (e.g., acomputer). The machine-readable medium may include, but is not limitedto, magnetic storage medium (e.g., floppy diskette); optical storagemedium (e.g., CD-ROM); magneto-optical storage medium; read-only memory(ROM); random-access memory (RAM); erasable programmable memory (e.g.,EPROM and EEPROM); flash memory; or another type of medium suitable forstoring electronic instructions.

Additionally, some embodiments may be practiced in distributed computingenvironments where the machine-readable medium is stored on and/orexecuted by more than one computer system. In addition, the informationtransferred between computer systems may either be pulled or pushedacross the communication medium connecting the computer systems.

Computer processing components used in implementation of variousembodiments of the invention include one or more general-purposeprocessing devices such as a microprocessor or central processing unit,a controller, graphical processing unit (GPU), cell computer, or thelike. Alternatively, such digital processing components may include oneor more special-purpose processing devices such as a digital signalprocessor (DSP), an application specific integrated circuit (ASIC), afield programmable gate array (FPGA), or the like. In particularembodiments, for example, the digital processing device may be a networkprocessor having multiple processors including a core unit and multiplemicroengines. Additionally, the digital processing device may includeany combination of general-purpose processing device(s) andspecial-purpose processing device(s).

Although the operations of the method(s) herein are shown and describedin a particular order, the order of the operations of each method may bealtered so that certain operations may be performed in an inverse orderor so that certain operation may be performed, at least in part,concurrently with other operations. In another embodiment, instructionsor sub-operations of distinct operations may be in an intermittentand/or alternating manner.

Where a component (e.g. a software module, processor, assembly, device,circuit, etc.) is referred to above, unless otherwise indicated,reference to that component (including a reference to a “means”) shouldbe interpreted as including as equivalents of that component anycomponent which performs the function of the described component (i.e.that is functionally equivalent), including components which are notstructurally equivalent to the disclosed structure which performs thefunction in the illustrated exemplary embodiments of the invention.

As will be apparent to those skilled in the art in light of theforegoing disclosure, many alterations and modifications are possible inthe practice of this invention without departing from the spirit orscope thereof. For example:

-   -   The above-described embodiments describe several features which        may be characteristics of each beam 159. By way of non-limiting        example, the procedures of block 72-78 for each loop of method        70 (FIG. 13) are performed for each beam 159 and FIG. 12 shows a        number of beams 159. In some embodiments, radiation delivery may        involve continuous movement of the radiation source with respect        to the subject over a given trajectory. In such embodiments, the        trajectory of movement of the radiation source with respect to        the subject may be described by a number of discrete sample        beams from along trajectory. Such sample beams may be sampled        sufficiently closely to one another such that the sum of the        dose contributions of the sample beams is representative of the        sum of the dose contributions from the continuously moving        radiation source. Such sample beams may be used in a manner        similar to that described herein for conventional discrete beams        and unless specifically described as being discrete, any        references to beam(s) herein should be understood to include        sample beams.    -   Referring to FIG. 4A, it will be appreciated by those skilled in        the art that the number of beam 159 is not required to be the        same in blocks 142 and 143. For example, it can be        computationally more efficient to have a relatively small number        of beams 159 when permitting manipulation of the estimated dose        in block 142. Then, in block 143, a larger number of beams 159        can be used to accurately determine the radiation delivery        parameters. In some embodiments, the number and/or location of        beams 159 may be one of the variables that is permitted to        change in a block 143 optimization process.    -   The discussion presented above suggests that there is a one to        one relationship between beamlets 164 and ray lines 163—i.e.        each beamlet 164 has a corresponding ray line 163. Such ray        lines 163 may pass through the center of their corresponding        beamlets 164. Using such ray lines 163, a relationship can be        established between particular beamlets and particular        voxels—e.g. dose-change beamlets can be identified as those        beamlets that have corresponding ray lines that project through        a dose modification voxel (see discussion of block 221 above).        It will be appreciated, however, that beamlets actually have a        two-dimensional shape. In some embodiments, it may be desirable        to model this two dimensional beamlet shape by accounting for        the impact of a beamlet on voxels other than merely the        particular voxels through which its corresponding ray line        passes. For example, in some rapid dose estimation embodiments        (e.g. in some embodiments of method 70 of FIG. 13) the ray lines        associated with particular convolved intensity values may        impinge on particular voxels at locations away from the centers        of the particular voxels and the dose contributions from those        convolved intensity values may be fractionally divided as        between the particular voxels and one or more of their        neighboring voxels. The fractional division of dose        contributions between the particular voxels and neighboring        voxels may depend on the location where the ray line impinges on        the particular voxels. For example, most of the fractional dose        contribution may be added to a particular voxel intersected by a        ray line and the remaining dose contribution may be divided        between the neighboring voxels, with neighboring voxels        relatively close to the location of intersection receiving a        greater dose contribution than neighboring voxels that are        relatively far from the location of intersection.    -   In some rapid dose estimation embodiments (e.g. in some        embodiments of method 70 of FIG. 13), it may be the case that        multiple ray lines 163 from a single beam of convolved        intensities impinge on a single voxel. In such cases, the dose        contribution added to the voxel may be some form of average or        interpolation of the dose contributions that would be predicted        by each of the individual convolved intensity values.    -   The discussion presented above suggests that there is a one to        one relationship between beamlets 164 and ray lines 163—i.e.        each beamlet 164 has a corresponding ray line 163 which may pass        through its center. However, in other embodiments, for each        beam, ray lines could additionally or alternatively have a one        to one relationship with voxels—i.e. each voxel could have a        corresponding ray line that extends from the center of the voxel        toward the radiation source location for that particular beam.        In such embodiments, the block 221 (FIG. 4B) process for        identification of dose-change beamlets could involve tracing        rays from the block 220 dose modification voxels onto the        two-dimensional grids 162 of beamlets 164—i.e. dose-change        beamlets could be identified as those through which a ray line        projects. In some embodiments, it may be desirable to model the        three-dimensional voxel shape by accounting for the impact of a        voxel on beamlets other than merely the particular beamlets        through which its corresponding ray line passes. For example, in        some embodiments of method 18 (FIG. 4B), the ray lines        associated with particular dose modification voxels may impinge        on particular beamlets at locations away from the centers of the        particular beamlets and the block 223 intensity value        adjustments may be fractionally divided as between the        particular beamlets and one or more of their neighboring        beamlets. The fractional division of intensity adjustments        between the particular beamlets and neighboring beamlets may        depend on the location where the ray line impinges on the        particular beamlets. For example, most of the fractional        intensity value adjustment may be made to a particular beamlet        intersected by a ray line and the remaining intensity value        adjustment may be divided between the neighboring beamlets, with        neighboring beamlets relatively close to the location of        intersection receiving a greater fraction of the intensity value        adjustment than neighboring beamlets that are relatively far        from the location of intersection.    -   In some embodiments, ray lines for each beam may have a one to        one association with voxels and ray lines may extend from the        center of voxels to the radiation source location for that        particular beam. In such embodiments, it may be the case (e.g.        in block 221 of method 18 (FIG. 4B)) that multiple ray lines        from multiple voxels impinge on a single beamlet. In such cases,        the block 223 intensity value adjustment to the beamlet may be        some form of average or interpolation of the intensity value        adjustments that would be applied by each of the individual        voxels.    -   One technique for rapid estimation of achievable dose described        above involves convolving a two-dimensional intensity        distribution i(x,y) and the two-dimensional dose estimate kernel        k(x,y) and then projecting the convolved intensity values of the        resultant two-dimensional convolved intensity distribution        f(x,y) along corresponding ray lines by adding the convolved        intensity values as dose contributions to voxels intersected by        the ray lines. In some embodiments, it may be desirable to        compute convolved intensity distributions f₁(x,y), f₂(x,y), . .        . for a number of different dose estimate kernels k₁(x,y),        k₂(x,y), . . . , where the different dose estimate kernels can        be used to model different tissue densities and their        corresponding different scattering patterns. Then, when        estimating achievable dose for a particular voxel (e.g. when        adding convolved intensity values as dose contributions to the        particular voxel), the tissue density of the particular voxel p        can be used to select convolved intensity values from a        convolved intensity distribution f_(p)(x,y) computed using a        dose estimate kernel k_(p)(x,y) which corresponds to the tissue        density.

In the foregoing description, the invention has been described withreference to specific exemplary embodiments thereof. It will, however,be evident that various modifications and changes may be made theretowithout departing from the broader spirit and scope of the invention.The description and drawings are, accordingly, to be regarded in anillustrative sense rather than a restrictive sense. While a number ofexemplary aspects and embodiments have been discussed above, those ofskill in the art will recognize certain modifications, permutations,additions and sub-combinations thereof. It is therefore intended thatthe following appended claims and claims hereafter introduced areinterpreted to include all such modifications, permutations, additionsand sub-combinations as are within their true spirit and scope.

1. A method for permitting manipulation of an achievable dosedistribution estimate deliverable by a radiation delivery apparatus forproposed treatment of a subject, the achievable dose distributionestimate defined over a three-dimensional range of voxels with a dosevalue for each voxel, the method comprising: (a) determining a dosemodification voxel for which it is desired to modify the dose value anddetermining a corresponding magnitude of desired dose modification; (b)for each of a plurality of beams: (i) characterizing the beam as atwo-dimensional array of beamlets, wherein each beamlet is associatedwith a corresponding intensity value and a ray line representing aprojection of the beamlet into space; and (ii) identifying one or moredose-change beamlets which have associated ray lines that intersect thedose modification voxel; (c) modifying the intensity values of theidentified dose-change beamlets based on the magnitude of desired dosemodification, wherein modifying the intensity value of the identifieddose-change beamlets comprises, for each of the identified dose-changebeamlets, modifying the intensity value of the identified dose-changebeamlet by a corresponding amount, the corresponding amount based on themagnitude of the desired dose modification; and (d) updating theachievable dose distribution estimate to account for the modifiedintensity values of the identified dose-change beamlets.
 2. A methodaccording to claim 1 wherein determining the dose modification voxelcomprises: receiving, as input, a requested modification to a dosequality metric; and using the requested modification to the dose qualitymetric to determine the dose modification voxel. 3.-6. (canceled)
 7. Amethod according to claim 2 wherein using the requested modification tothe dose quality metric to determine the dose modification voxelcomprises solving an inverted dose quality metric function thatexpresses coordinates and magnitudes of dose in terms of values of thedose quality metric.
 8. A method according to claim 2 wherein the dosequality metric comprises a DVH curve associated with a tissue structurein the subject and wherein using the requested modification to the dosequality metric to determine the dose modification voxel comprisesidentifying a voxel in the tissue structure of the subject to be thedose modification voxel.
 9. A method according to claim 8 whereinidentifying the voxel in the tissue structure of the subject to be thedose modification voxel comprises identifying all of the voxels in thetissue structure of the subject to be dose modification voxels andperforming steps (b), (c) and (d) for each of the dose modificationvoxels.
 10. A method according to claim 8 wherein identifying the voxelin the tissue structure of the subject to be the dose modification voxelcomprises: receiving image data for the subject, the image datacomprising an image of the tissue structure; and associating particularvoxels with the tissue structure based on the image data.
 11. A methodaccording to claim 2 wherein the dose quality metric comprises a DVHcurve and wherein using the requested modification to the dose qualitymetric to determine the dose modification voxel comprises: identifying alocation of the requested modification on the DVH curve to have a dosevalue D_selected; and identifying a voxel in the achievable dosedistribution estimate having a dose value in a range D_selected±Δ to bethe dose modification voxel, where Δ is a range parameter.
 12. A methodaccording to claim 11 wherein using the requested modification to thedose quality metric to determine the dose modification voxel comprises:if an attempt to identify the voxel in the achievable dose distributionestimate having the dose value in the range D_selected±Δ is notsuccessful, increasing the range parameter Δ and repeating the attemptto identify the voxel with the increased range parameter Δ.
 13. A methodaccording to claim 11 wherein identifying the voxel in the achievabledose distribution estimate having the dose value in the rangeD_selected±Δ to be the dose modification voxel comprises identifying aplurality of candidate dose modification voxels having dose values inthe range D_selected±Δ.
 14. A method according to claim 13 wherein ifthe plurality of candidate dose modification voxels comprise a number ofcandidate dose modification voxels that is greater than a thresholdnumber V_(max), then the method comprises decreasing the range parameterΔ and repeating the attempt to identify the voxel in the achievable dosedistribution estimate having the dose value in the range D_selected±Δ tobe the dose modification voxel with the decreased range parameter Δ.15.-19. (canceled)
 20. A method according to claim 1 comprisingdetermining one or more secondary dose modification voxels andcorresponding magnitudes of desired dose modification for the secondarydose modification voxels and treating the secondary dose modificationvalues as dose modification voxels when performing steps (b), (c) and(d).
 21. A method according to claim 20 wherein determining one or moresecondary dose modification voxels comprises determining the one or moresecondary dose modification voxels to be in a marginal region proximateto the dose modification voxel.
 22. A method according to claim 20wherein the corresponding magnitudes of desired dose modification forthe secondary dose modification voxels are less than the magnitude ofthe desired dose modification for the dose modification voxel.
 23. Amethod according to claim 1 wherein determining the magnitude of thedesired dose modification comprises determining the magnitude to be oneor more of: a fraction f (0≦f≦1) of the dose value for the dosemodification voxel; a fraction f (0≦f≦1) of a maximum dose restrictionfor a tissue structure at the location of the dose modification voxel; afraction f (0≦f≦1) of a prescription dose amount for a target tissuestructure at the location of the dose modification voxel; an amountproportional to movement of a computer pointing device; an amount inputby an operator; an operator-configurable fixed amount; a fixed amountthat is a parameter of a system on which the method is performed.24.-28. (canceled)
 29. A method according to claim 1 wherein modifyingthe intensity values of one or more of the dose-change beamletscomprises determining magnitudes of intensity value changes for the oneor more dose-change beamlets according to a function that is dependenton the magnitude of desired dose modification and the number of the oneor more dose-change beamlets, and wherein the function is proportionalto magnitude of desired dose modification and inversely proportional tothe number of the one or more dose-change beamlets.
 30. A methodaccording to claim 1 wherein modifying the intensity values of one ormore of the dose-change beamlets comprises subjecting proposed intensityvalue modifications to one or more intensity restrictions.
 31. A methodaccording to claim 30 wherein the one or more intensity restrictionscomprise one or more of: the intensity values of the one or moredose-change beamlets must be greater than a minimum threshold; theintensity values of the one or more dose-change beamlets must be lessthan a maximum threshold; a spatial variation between the intensityvalues of the one or more dose-change beamlets and the intensity valuesof one or more neighboring beamlets must be less than a maximumvariation threshold.
 32. (canceled)
 33. A method according to claim 1comprising, for each of the plurality of beams and for each of the oneor more dose-change beamlets, determining one or more secondarydose-change beamlets and treating the secondary dose-change beamlets asdose-change beamlets when performing steps (c) and (d).
 34. A methodaccording to claim 33 wherein, for each of the plurality of beams andfor each of the one or more dose-change beamlets, determining one ormore secondary dose-change beamlets comprises determining the one ormore secondary dose-change beamlets to be in a marginal region proximateto the dose-change beamlet.
 35. A method according to claim 34 whereinmodifying the intensity values of one or more of the dose changebeamlets comprises, for each of the one or more dose change beamlets,modifying the intensity values of the secondary dose change beamlets inthe marginal region proximate to the dose-change beamlet by magnitudesless than a magnitude of the change to the dose-change beamlet.
 36. Amethod according to claim 1 wherein updating the achievable dosedistribution estimate comprises using a dose estimation technique todetermine dose contributions attributable to the modified intensityvalues of the one or more dose-change beamlets, the dose estimationtechnique comprising one or more of: Monte Carlo, collapsed coneconvolution, pencil beam, anisotropic analytical algorithm and Boltzmanequation solvers. 37.-38. (canceled)
 39. A method according to claim 1wherein updating the achievable dose distribution estimate comprises,for each of the plurality of beams comprising one or more dose changebeamlets: convolving the intensity values of the two-dimensional arrayof beamlets with a two-dimensional dose estimate kernel to obtain atwo-dimensional convolved intensity distribution, the two-dimensionalconvolved intensity distribution comprising a convolved intensity valuefor each beamlet; and for each beamlet in the two-dimensional array ofbeamlets: identifying voxels that are intersected by the ray lineassociated with the beamlet; and adding a dose contribution to theintersected voxels, the added dose contribution based on the convolvedintensity value of the beamlet.
 40. A method according to claim 39wherein the dose estimate kernel comprises a two-dimensional pointspread function.
 41. A method according to claim 39 wherein the doseestimate kernel comprises a linear combination of two dimensional pointspread functions.
 42. (canceled)
 43. A method according to claim 39wherein convolving the intensity values of the two-dimensional array ofbeamlets with the two-dimensional dose estimate kernel comprises:multiplying a Fourier transform of the intensity values of thetwo-dimensional array of beamlets with a Fourier transform of thetwo-dimensional dose estimate kernel to obtain a Fourier multiplicationresult; and determining an inverse Fourier transform of the Fouriermultiplication result to obtain the two-dimensional convolved intensitydistribution.
 44. (canceled)
 45. A method according to claim 39 wherein,in cases where a plurality of ray lines from a single beam intersect aparticular voxel, adding the dose contribution to the particular voxelcomprises adding the dose contribution based on a linear combination ofthe convolved intensity values of the plurality of beamletscorresponding to the plurality of ray lines.
 46. A method according toclaim 39 wherein, for each beamlet in the two-dimensional array ofbeamlets and for each intersected voxel, the added dose contribution isbased on the convolved intensity value of the beamlet multiplied by anattenuation factor, the attenuation factor decreasing with a depth ofthe intersected voxel within the subject. 47.-48. (canceled)
 49. Amethod according to claim 1 wherein updating the achievable dosedistribution estimate comprises, for each of the plurality of beamscomprising one or more dose change beamlets: convolving the intensityvalues of the two-dimensional array of beamlets with a plurality oftwo-dimensional dose estimate kernels to obtain a correspondingplurality of two-dimensional convolved intensity distributions, eachtwo-dimensional convolved intensity distribution comprising a convolvedintensity value for each beamlet, wherein each dose estimate kernel isassociated with a different range of tissue densities; and for eachbeamlet in the two-dimensional array of beamlets: identifying voxelsthat are intersected by the ray line associated with the beamlet; andadding a dose contribution to the intersected voxels, the dosecontribution for any one intersected voxel based on the convolvedintensity value of the beamlet from one of the plurality oftwo-dimensional convolved intensity distributions, the one of theplurality of two-dimensional convolved intensity distributions selectedbased on tissue density of the one intersected voxel.
 50. A methodaccording to claim 1 wherein updating the achievable dose distributionestimate comprises scaling the updated achievable dose distributionestimate such that the updated achievable dose distribution estimatemore closely approximates the magnitude of desired dose modificationcorresponding to the dose modification voxel.
 51. A method according toclaim 1 wherein updating the achievable dose distribution estimatecomprises subjecting the updated achievable dose distribution to one ormore dose restrictions.
 52. A method according to claim 51 wherein theone or more dose restrictions comprise one or more of: the updatedachievable dose distribution must not reduce dose in voxelscorresponding to target tissue structures in the subject below a minimumtarget structure threshold; and the updated achievable dose distributionmust not increase dose in voxels corresponding to healthy tissuestructures in the subject above a maximum healthy structure threshold.53. A method according to claim 51 wherein, if subjecting the updatedachievable dose distribution to one or more dose restrictions concludesthat there is a violation of any dose restriction, then, the methodcomprises addressing the violation of the dose restriction, whereinaddressing the violation of the dose restriction comprises one or moreof: rejecting the update to the achievable dose distribution estimate;and adjusting the magnitude of the desired dose modificationcorresponding to the dose modification voxel and repeating steps (b),(c) and (d) with the adjusted magnitude.
 54. A method according to claim51 wherein, if subjecting the updated achievable dose distribution toone or more dose restrictions concludes that there is a violation of anydose restriction, then, the method comprises: addressing the violationof the dose restriction, wherein addressing the violation of the doserestriction comprises: determining one or more restriction violatingvoxels which cause the updated dose distribution to violate the doserestriction and one or more corresponding desired dose changemagnitudes; repeating steps (b), (c) and (d) with the one or morerestriction violating voxels and the one or more corresponding desireddose change magnitudes in place of the dose modification voxel and thecorresponding magnitude of the desired dose modification; re-subjectingthe updated achievable dose distribution to the one or more doserestrictions; and repeating addressing the violation of the doserestriction until subjecting the updated achievable dose distribution toone or more dose restrictions concludes that there is not a violation ofany dose restriction.
 55. A method according to claim 1 comprising,after updating the achievable dose distribution estimate, determiningone or more updated dose quality metrics using the updated achievabledose distribution estimate.
 56. A method according to claim 55 whereindetermining one or more updated dose quality metrics comprisessubjecting at least one updated dose quality metric to one or more dosequality metric restrictions.
 57. A method according to claim 56 whereinthe one or more dose quality metric restrictions comprise one or moreof: the at least one updated dose quality metric must have a minimumpercentage volume of a target structure with dose above a minimum targetstructure threshold; and the at least one updated dose quality metricmust have a minimum percentage volume of a healthy tissue structure withdose lower than a maximum healthy tissue structure threshold. 58.-59.(canceled)
 60. A method according to claim 1 comprising, for each of theplurality of beams, initializing the intensity values of the beamlets inthe two-dimensional array of beamlets, wherein initializing theintensity values of the beamlets in the two-dimensional array ofbeamlets comprises one or more of: setting all intensity values to zero;setting intensity values according to a random process; settingintensity values such that an approximate sphere of dose encompassestarget tissue structures; setting intensity values for beamlets havingray lines that intersect target structures to be a first positive valueand setting intensity values for other beamlets to have a lower value;setting intensity values such that a resultant dose distributionestimate has a maximum dose higher than a threshold; and settingintensity values for all or a subset of the beamlets based on a functionof a prescription dose for a target structure.
 61. A method according toclaim 1 comprising, after updating the achievable dose distributionestimate, determining one or more radiation delivery parameters based onthe updated achievable dose estimate, the one or more radiation deliveryparameters suitable for use by the radiation delivery apparatus fortreatment of the subject.
 62. A method according to claim 61 whereindetermining one or more radiation delivery parameters based on theupdated achievable dose estimate comprises performing an iterativeoptimization process.
 63. A method according to claim 61 whereinperforming the iterative optimization process comprises optimizing theone or more radiation delivery parameters which will provide anoptimized dose distribution estimate similar within an acceptable rangeto the updated achievable dose estimate.
 64. A method according to claim62 wherein performing the iterative optimization process comprisesestimating an optimized dose distribution over a three-dimensional rangeof voxels resulting from an optimization beam having a spatially varyingtwo-dimensional optimization intensity distribution characterized by atwo-dimensional array of optimization beamlets wherein each optimizationbeamlet is associated with a corresponding optimization intensity value,the estimating comprising: associating an optimization ray line witheach optimization beamlet, the optimization ray line representing aprojection of the optimization beamlet into space; convolving thetwo-dimensional optimization intensity distribution with atwo-dimensional optimization dose estimate kernel to obtain atwo-dimensional optimization convolved intensity distribution, thetwo-dimensional optimization convolved intensity distribution comprisingan optimization convolved intensity value for each optimization beamlet;and for each optimization beamlet in the two-dimensional array ofoptimization beamlets: identifying voxels in the three-dimensional rangeof voxels that are intersected by the optimization ray line associatedwith the optimization beamlet; and adding an optimization dosecontribution to the intersected voxels, the added optimization dosecontribution based on the optimization convolved intensity value of theoptimization beamlet.
 65. A system for permitting manipulation of anachievable dose distribution estimate deliverable by a radiationdelivery apparatus for proposed treatment of a subject, the achievabledose distribution estimate defined over a three-dimensional range ofvoxels with a dose value for each voxel, the system comprising acontroller configured to: determine a dose modification voxel for whichit is desired to modify the dose value and a corresponding magnitude ofdesired dose modification; for each of a plurality of beams:characterize the beam as a two-dimensional array of beamlets, whereineach beamlet is associated with a corresponding intensity value and aray line representing a projection of the beamlet into space; andidentify one or more dose-change beamlets which have associated raylines that intersect the dose modification voxel; modify the intensityvalues of the identified dose-change beamlets based on the magnitude ofthe desired dose modification, wherein the controller is configured tomodify the intensity value of the identified dose change beamlets by,for each of the identified dose-change beamlets, modifying the intensityvalue of the identified dose-change beamlet by a corresponding amount,the corresponding amount based on the magnitude of the desired dosemodification; and update the achievable dose distribution estimate toaccount for the modified intensity values of the identified dose-changebeamlets.
 66. A computer program product carrying instructions embodiedin a non-transitory computer-readable medium, the instructions whenexecuted by a suitable processor cause the processor to perform a methodfor permitting manipulation of an achievable dose distribution estimatedeliverable by a radiation delivery apparatus for proposed treatment ofa subject, the achievable dose distribution estimate defined over athree-dimensional range of voxels with a dose value for each voxel, themethod comprising the method of claim
 1. 67. A method for estimating adose distribution over a three-dimensional range of voxels proposed tocontain a subject resulting from one or more beams, each beam comprisinga spatially varying two-dimensional intensity distribution characterizedby a two-dimensional array of beamlets wherein each beamlet isassociated with a corresponding intensity value, the method comprising,for each of the one or more beams: associating a ray line with eachbeamlet, the ray line representing a projection of the beamlet intospace; convolving the two-dimensional intensity distribution with atwo-dimensional dose estimate kernel to obtain a two-dimensionalconvolved intensity distribution, the two-dimensional convolvedintensity distribution comprising a convolved intensity value for eachbeamlet; and for each beamlet in the two-dimensional array of beamlets:identifying voxels in the three-dimensional range of voxels that areintersected by the ray line associated with the beamlet; and adding adose contribution to the intersected voxels, the added dose contributionbased on the convolved intensity value of the beamlet. 68.-81.(canceled)
 82. A system for estimating a dose distribution over athree-dimensional range of voxels proposed to contain a subjectresulting from one or more beams, each beam comprising a spatiallyvarying two-dimensional intensity distribution characterized by atwo-dimensional array of beamlets wherein each beamlet is associatedwith a corresponding intensity value, the system comprising a controllerconfigured to, for each of the one or more beams: associate a ray linewith each beamlet, the ray line representing a projection of the beamletinto space; convolve the two-dimensional intensity distribution with atwo-dimensional dose estimate kernel to obtain a two-dimensionalconvolved intensity distribution, the two-dimensional convolvedintensity distribution comprising a convolved intensity value for eachbeamlet; and for each beamlet in the two-dimensional array of beamlets:identify voxels in the three-dimensional range of voxels that areintersected by the ray line associated with the beamlet; and add a dosecontribution to the intersected voxels, the added dose contributionbased on the convolved intensity value of the beamlet.
 83. A computerprogram product carrying instructions embodied in a non-transitorycomputer-readable medium, the instructions when executed by a suitableprocessor cause the processor to perform a method for estimating a dosedistribution over a three-dimensional range of voxels proposed tocontain a subject resulting from one or more beams, each beam comprisinga spatially varying two-dimensional intensity distribution characterizedby a two-dimensional array of beamlets wherein each beamlet isassociated with a corresponding intensity value, the method comprisingthe method of claim
 67. 84.-88. (canceled)